Advertisement

Immunomodulatory Molecules of the Immune System

  • Yvonne M. Saenger
  • Robert R. Jenq
  • Miguel-Angel Perales

Keywords

Antitumor Immunity Isolate Limb Perfusion Tumor Immunotherapy Herpes Virus Entry Mediator Immunomodulatory Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Perales MA, Blachere NE, Engelhorn ME et al. Strategies to overcome immune ignorance and tolerance. Semin Cancer Biol 2002; 12: 63–71.PubMedCrossRefGoogle Scholar
  2. 2.
    Jager E, Ringhoffer M, Karbach J et al. Inverse relationship of melanocyte differentiation antigen expression in melanoma tissues and CD8+ cytotoxic-T-cell responses: evidence for immunoselection of antigen-loss variants in vivo. Int J Cancer 1996; 66: 470–476.PubMedCrossRefGoogle Scholar
  3. 3.
    Dessureault S, Graham F, Gallinger S. B7–1 gene transfer into human cancer cells by infection with an adenovirus-B7 (Ad-B7) expression vector. Ann Surg Oncol 1996; 3: 317–324.PubMedCrossRefGoogle Scholar
  4. 4.
    Wojtowicz-Praga S. Reversal of tumor-induced immunosuppression: a new approach to cancer therapy [see comments]. J Immunother 1997; 20: 165–177.PubMedCrossRefGoogle Scholar
  5. 5.
    Bretscher P, Cohn M. A theory of self-nonself discrimination. Science 1970; 169: 1042–1049.PubMedCrossRefGoogle Scholar
  6. 6.
    Lafferty KJ, Woolnough J. The origin and mechanism of the allograft reaction. Immunol Rev 1977; 35: 231–262.PubMedCrossRefGoogle Scholar
  7. 7.
    Baxter AG, Hodgkin PD. Activation rules: the two-signal theories of immune activation. Nat Rev Immunol 2002; 2: 439–446.PubMedGoogle Scholar
  8. 8.
    Jenkins MK, Schwartz RH. Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J Exp Med 1987; 165: 302–319.PubMedCrossRefGoogle Scholar
  9. 9.
    Quill H, Schwartz RH. Stimulation of normal inducer T cell clones with antigen presented by purified Ia molecules in planar lipid membranes: specific induction of a long-lived state of proliferative nonresponsiveness. J Immunol 1987; 138: 3704–3712.PubMedGoogle Scholar
  10. 10.
    Vesosky B, Hurwitz AA. Modulation of costimulation to enhance tumor immunity. Cancer Immunol Immunother 2003; 52: 663–669.PubMedCrossRefGoogle Scholar
  11. 11.
    Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol 2001; 19: 565–594.PubMedCrossRefGoogle Scholar
  12. 12.
    Chen L. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 2004; 4: 336–347.PubMedCrossRefGoogle Scholar
  13. 13.
    Contardi E, Palmisano GL, Tazzari PL et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer 2005.Google Scholar
  14. 14.
    Taylor PA, Lees CJ, Fournier S et al. B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via R-T interactions. J Immunol 2004; 172: 34–39.PubMedGoogle Scholar
  15. 15.
    Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 1993; 259: 368–370.PubMedCrossRefGoogle Scholar
  16. 16.
    Chen L, Ashe S, Brady WA et al. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71: 1093–1102.PubMedCrossRefGoogle Scholar
  17. 17.
    Yokochi T, Holly RD, Clark EA. B lymphoblast antigen (BB-1) expressed on Epstein-Barr virus-activated B cell blasts, B lymphoblastoid cell lines, and Burkitt’s lymphomas. J Immunol 1982; 128: 823–827.PubMedGoogle Scholar
  18. 18.
    Azuma M, Ito D, Yagita H et al. B70 antigen is a second ligand for CTLA-4 and CD28. Nature 1993; 366: 76–79.PubMedCrossRefGoogle Scholar
  19. 19.
    Freeman GJ, Borriello F, Hodes RJ et al. Murine B7–2, an alternative CTLA-4 counter-receptor that costimulates T cell proliferation and interleukin 2 production. J. Exp. Med. 1993; 178: 2185–2192.PubMedCrossRefGoogle Scholar
  20. 20.
    Freeman GJ, Gribben JG, Boussiotis VA et al. Cloning of B7–2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 1993; 262: 909–911.PubMedCrossRefGoogle Scholar
  21. 21.
    Martin PJ, Ledbetter JA, Morishita Y et al. A 44 kilodalton cell surface homodimer regulates interleukin 2 production by activated human T lymphocytes. J Immunol 1986; 136: 3282–3287.PubMedGoogle Scholar
  22. 22.
    Boise LH, Minn AJ, Noel PJ et al. CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL. Immunity 1995; 3: 87–98.PubMedCrossRefGoogle Scholar
  23. 23.
    Brunet JF, Denizot F, Luciani MF et al. A new member of the immunoglobulin superfamily–CTLA-4. Nature 1987; 328: 267–270.PubMedCrossRefGoogle Scholar
  24. 24.
    Linsley PS, Brady W, Urnes M et al. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med 1991; 174: 561–569.PubMedCrossRefGoogle Scholar
  25. 25.
    Krummel MF, Allison JP. CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995; 182: 459–465.PubMedCrossRefGoogle Scholar
  26. 26.
    Thompson CB, Allison JP. The emerging role of CTLA-4 as an immune attenuator. Immunity 1997; 7: 445–450.PubMedCrossRefGoogle Scholar
  27. 27.
    Scheipers P, Reiser H. Fas-independent death of activated CD4(+) T lymphocytes induced by CTLA-4 crosslinking. Proc Natl Acad Sci U S A 1998; 95: 10083–10088.PubMedCrossRefGoogle Scholar
  28. 28.
    Walunas TL, Lenschow DJ, Bakker CY et al. CTLA-4 can function as a negative regulator of T cell activation. Immunity 1994; 1: 405–413.PubMedCrossRefGoogle Scholar
  29. 29.
    Tivol EA, Borriello F, Schweitzer AN et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995; 3: 541–547.PubMedCrossRefGoogle Scholar
  30. 30.
    Waterhouse P, Penninger JM, Timms E et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 1995; 270: 985–988.PubMedCrossRefGoogle Scholar
  31. 31.
    Chambers CA, Cado D, Truong T, Allison JP. Thymocyte development is normal in CTLA-4-deficient mice. Proc Natl Acad Sci U S A 1997; 94: 9296–9301.PubMedCrossRefGoogle Scholar
  32. 32.
    Egen JG, Kuhns MS, Allison JP. CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nat Immunol 2002; 3: 611–618.PubMedCrossRefGoogle Scholar
  33. 33.
    Pentcheva-Hoang T, Egen JG, Wojnoonski K, Allison JP. B7–1 and B7–2 selectively recruit CTLA-4 and CD28 to the immunological synapse. Immunity 2004; 21: 401–413.PubMedCrossRefGoogle Scholar
  34. 34.
    Perez VL, Van Parijs L, Biuckians A et al. Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 1997; 6: 411–417.PubMedCrossRefGoogle Scholar
  35. 35.
    Metz DP, Farber DL, Taylor T, Bottomly K. Differential role of CTLA-4 in regulation of resting memory versus naive CD4 T cell activation. J Immunol 1998; 161: 5855–5861.PubMedGoogle Scholar
  36. 36.
    Kuhns MS, Epshteyn V, Sobel RA, Allison JP. Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of CD4+ T cells. Proc Natl Acad Sci U S A 2000; 97: 12711–12716.PubMedCrossRefGoogle Scholar
  37. 37.
    Chen W, Jin W, Wahl SM. Engagement of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) induces transforming growth factor beta (TGF-beta) production by murine CD4(+) T cells. J Exp Med 1998; 188: 1849–1857.PubMedCrossRefGoogle Scholar
  38. 38.
    Jovasevic VM, Gorelik L, Bluestone JA, Mokyr MB. Importance of IL-10 for CTLA-4-mediated inhibition of tumor-eradicating immunity. J Immunol 2004; 172: 1449–1454.PubMedGoogle Scholar
  39. 39.
    Orabona C, Grohmann U, Belladonna ML et al. CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86. Nat Immunol 2004; 5: 1134–1142.PubMedCrossRefGoogle Scholar
  40. 40.
    Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295–302.PubMedCrossRefGoogle Scholar
  41. 41.
    Salomon B, Lenschow DJ, Rhee L et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000; 12: 431–440.PubMedCrossRefGoogle Scholar
  42. 42.
    Takahashi T, Tagami T, Yamazaki S et al. Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J Exp Med 2000; 192: 303–310.PubMedCrossRefGoogle Scholar
  43. 43.
    Berger CL, Tigelaar R, Cohen J et al. Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood 2005; 105: 1640–1647.PubMedCrossRefGoogle Scholar
  44. 44.
    Marshall NA, Christie LE, Munro LR et al. Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 2004; 103: 1755–1762.PubMedCrossRefGoogle Scholar
  45. 45.
    Kono K, Kawaida H, Takahashi A et al. CD4(+)CD25(high) regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother 2005; 1–8.Google Scholar
  46. 46.
    Wolf AM, Wolf D, Steurer M et al. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 2003; 9: 606–612.PubMedGoogle Scholar
  47. 47.
    Wolf D, Wolf AM, Rumpold H et al. The Expression of the Regulatory T Cell-Specific Forkhead Box Transcription Factor FoxP3 Is Associated with Poor Prognosis in Ovarian Cancer. Clin Cancer Res 2005; 11: 8326–8331.PubMedCrossRefGoogle Scholar
  48. 48.
    Hurwitz AA, Kwon ED, van Elsas A. Costimulatory wars: the tumor menace. Curr Opin Immunol 2000; 12: 589–596.PubMedCrossRefGoogle Scholar
  49. 49.
    Li Y, McGowan P, Hellstrom I et al. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J Immunol 1994; 153: 421–428.PubMedGoogle Scholar
  50. 50.
    Townsend SE, Su FW, Atherton JM, Allison JP. Specificity and longevity of antitumor immune responses induced by B7-transfected tumors. Cancer Res 1994; 54: 6477–6483.PubMedGoogle Scholar
  51. 51.
    Baskar S, Glimcher L, Nabavi N et al. Major histocompatibility complex class II+B7–1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice. J Exp Med 1995; 181: 619–629.PubMedCrossRefGoogle Scholar
  52. 52.
    Yang G, Hellstrom KE, Hellstrom I, Chen L. Antitumor immunity elicited by tumor cells transfected with B7–2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol 1995; 154: 2794–2800.PubMedGoogle Scholar
  53. 53.
    Hull GW, McCurdy MA, Nasu Y et al. Prostate cancer gene therapy: comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7–1 for in situ gene therapy and gene-modified, cell-based vaccines. Clin Cancer Res 2000; 6: 4101–4109.PubMedGoogle Scholar
  54. 54.
    Chen L, McGowan P, Ashe S et al. Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med 1994; 179: 523–532.PubMedCrossRefGoogle Scholar
  55. 55.
    Ostrand-Rosenberg S. Tumor immunotherapy: the tumor cell as an antigen-presenting cell. Curr Opin Immunol 1994; 6: 722–727.PubMedCrossRefGoogle Scholar
  56. 56.
    Hurwitz AA, Townsend SE, Yu TF et al. Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma. Int J Cancer 1998; 77: 107–113.PubMedCrossRefGoogle Scholar
  57. 57.
    Li Y, Hellstrom KE, Newby SA, Chen L. Costimulation by CD48 and B7–1 induces immunity against poorly immunogenic tumors. J Exp Med 1996; 183: 639–644.PubMedCrossRefGoogle Scholar
  58. 58.
    Johnston JV, Malacko AR, Mizuno MT et al. B7-CD28 costimulation unveils the hierarchy of tumor epitopes recognized by major histocompatibility complex class I-restricted CD8+ cytolytic T lymphocytes. J Exp Med 1996; 183: 791–800.PubMedCrossRefGoogle Scholar
  59. 59.
    Harding FA, Allison JP. CD28-B7 interactions allow the induction of CD8+ cytotoxic T lymphocytes in the absence of exogenous help. J Exp Med 1993; 177: 1791–1796.PubMedCrossRefGoogle Scholar
  60. 60.
    Houghton AN, Gold JS, Blachere NE. Immunity against cancer: lessons learned from melanoma. Curr Opin Immunol 2001; 13: 134–140.PubMedCrossRefGoogle Scholar
  61. 61.
    Li Y, Newby SA, Johnston JV et al. Protective immunity induced by B7/CD28-costimulated gamma delta T cells to the EL-4 lymphoma in allogenic athymic mice. J Immunol 1995; 155: 5705–5710.PubMedGoogle Scholar
  62. 62.
    Wu TC, Huang AY, Jaffee EM et al. A reassessment of the role of B7–1 expression in tumor rejection. J Exp Med 1995; 182: 1415–1421.PubMedCrossRefGoogle Scholar
  63. 63.
    Antonia SJ, Seigne J, Diaz J et al. Phase I trial of a B7–1 (CD80) gene modified autologous tumor cell vaccine in combination with systemic interleukin-2 in patients with metastatic renal cell carcinoma. J Urol 2002; 167: 1995–2000.PubMedCrossRefGoogle Scholar
  64. 64.
    Raez LE, Cassileth PA, Schlesselman JJ et al. Induction of CD8 T-cell-Ifn-gamma response and positive clinical outcome after immunization with gene-modified allogeneic tumor cells in advanced non-small-cell lung carcinoma. Cancer Gene Ther 2003; 10: 850–858.PubMedCrossRefGoogle Scholar
  65. 65.
    Dols A, Smith JW, 2nd, Meijer SL et al. Vaccination of women with metastatic breast cancer, using a costimulatory gene (CD80)-modified, HLA-A2-matched, allogeneic, breast cancer cell line: clinical and immunological results. Hum Gene Ther 2003; 14: 1117–1123.PubMedCrossRefGoogle Scholar
  66. 66.
    Dols A, Meijer SL, Hu HM et al. Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogeneic tumor cells. J Immunother 2003; 26: 163–170.PubMedCrossRefGoogle Scholar
  67. 67.
    Horig H, Lee DS, Conkright W et al. Phase I clinical trial of a recombinant canarypoxvirus (ALVAC) vaccine expressing human carcinoembryonic antigen and the B7.1 co-stimulatory molecule. Cancer Immunol Immunother 2000; 49: 504–514.PubMedCrossRefGoogle Scholar
  68. 68.
    von Mehren M, Arlen P, Tsang KY et al. Pilot study of a dual gene recombinant avipox vaccine containing both carcinoembryonic antigen (CEA) and B7.1 transgenes in patients with recurrent CEA-expressing adenocarcinomas. Clin Cancer Res 2000; 6: 2219–2228.Google Scholar
  69. 69.
    Marshall JL, Gulley JL, Arlen PM et al. Phase I study of sequential vaccinations with fowlpox-CEA(6D)-TRICOM alone and sequentially with vaccinia-CEA(6D)-TRICOM, with and without granulocyte-macrophage colony-stimulating factor, in patients with carcinoembryonic antigen-expressing carcinomas. J Clin Oncol 2005; 23: 720–731.PubMedCrossRefGoogle Scholar
  70. 70.
    Kaufman HL, Deraffele G, Mitcham J et al. Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J Clin Invest 2005; 115: 1903–1912.PubMedCrossRefGoogle Scholar
  71. 71.
    Hodge JW, McLaughlin JP, Abrams SI et al. Admixture of a recombinant vaccinia virus containing the gene for the costimulatory molecule B7 and a recombinant vaccinia virus containing a tumor-associated antigen gene results in enhanced specific T-cell responses and antitumor immunity. Cancer Res 1995; 55: 3598–3603.PubMedGoogle Scholar
  72. 72.
    Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996; 271: 1734–1736.PubMedCrossRefGoogle Scholar
  73. 73.
    Kwon ED, Hurwitz AA, Foster BA et al. Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc Natl Acad Sci U S A 1997; 94: 8099–8103.PubMedCrossRefGoogle Scholar
  74. 74.
    Hurwitz AA, Yu TF, Leach DR, Allison JP. CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma. Proc Natl Acad Sci U S A 1998; 95: 10067–10071.PubMedCrossRefGoogle Scholar
  75. 75.
    van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med 1999; 190: 355–366.CrossRefGoogle Scholar
  76. 76.
    van Elsas A, Sutmuller RP, Hurwitz AA et al. Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapy. J Exp Med 2001; 194: 481–489.CrossRefGoogle Scholar
  77. 77.
    Hurwitz AA, Foster BA, Kwon ED et al. Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res 2000; 60: 2444–2448.PubMedGoogle Scholar
  78. 78.
    Gregor PD, Wolchok JD, Ferrone CR et al. CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems. Vaccine 2004; 22: 1700–1708.PubMedCrossRefGoogle Scholar
  79. 79.
    Kwon ED, Foster BA, Hurwitz AA et al. Elimination of residual metastatic prostate cancer after surgery and adjunctive cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade immunotherapy. Proc Natl Acad Sci U S A 1999; 96: 15074–15079.PubMedCrossRefGoogle Scholar
  80. 80.
    Mokyr MB, Kalinichenko T, Gorelik L, Bluestone JA. Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res 1998; 58: 5301–5304.PubMedGoogle Scholar
  81. 81.
    Demaria S, Kawashima N, Yang AM et al. Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res 2005; 11: 728–734.PubMedGoogle Scholar
  82. 82.
    Pure E, Allison JP, Schreiber RD. Breaking down the barriers to cancer immunotherapy. Nat Immunol 2005; 6: 1207–1210.PubMedCrossRefGoogle Scholar
  83. 83.
    Maker AV, Attia P, Rosenberg SA. Analysis of the cellular mechanism of antitumor responses and autoimmunity in patients treated with ctla-4 blockade. J Immunol 2005; 175: 7746–7754.PubMedGoogle Scholar
  84. 84.
    Hodi FS, Mihm MC, Soiffer RJ et al. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A 2003; 100: 4712–4717.PubMedCrossRefGoogle Scholar
  85. 85.
    Phan GQ, Yang JC, Sherry RM et al. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A 2003; 100: 8372–8377.PubMedCrossRefGoogle Scholar
  86. 86.
    Attia P, Phan GQ, Maker AV et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 2005; 23: 6043–6053.PubMedCrossRefGoogle Scholar
  87. 87.
    Perales MA, Chapman PB. Immunizing against partially defined antigen mixtures, gangliosides, or peptides to induce antibody, T cell, and clinical responses. Cancer Chemother Biol Response Modif 2005; 22: 749–760.PubMedGoogle Scholar
  88. 88.
    Sanderson K, Scotland R, Lee P et al. Autoimmunity in a phase I trial of a fully human anti-cytotoxic T-lymphocyte antigen-4 monoclonal antibody with multiple melanoma peptides and Montanide ISA 51 for patients with resected stages III and IV melanoma. J Clin Oncol 2005; 23: 741–750.PubMedCrossRefGoogle Scholar
  89. 89.
    Maker AV, Phan GQ, Attia P et al. Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study. Ann Surg Oncol 2005; 12: 1005–1016.PubMedCrossRefGoogle Scholar
  90. 90.
    Ribas A, Camacho LH, Lopez-Berestein G et al. Antitumor Activity in Melanoma and Anti-Self Responses in a Phase I Trial With the Anti-Cytotoxic T Lymphocyte-Associated Antigen 4 Monoclonal Antibody CP-675,206. J Clin Oncol 2005.Google Scholar
  91. 91.
    Blansfield JA, Beck KE, Tran K et al. Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 2005; 28: 593–598.PubMedCrossRefGoogle Scholar
  92. 92.
    Hutloff A, Dittrich AM, Beier KC et al. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 1999; 397: 263–266.PubMedCrossRefGoogle Scholar
  93. 93.
    Liu X, Bai XF, Wen J et al. B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo. J Exp Med 2001; 194: 1339–1348.PubMedCrossRefGoogle Scholar
  94. 94.
    Wallin JJ, Liang L, Bakardjiev A, Sha WC. Enhancement of CD8+ T cell responses by ICOS/B7h costimulation. J Immunol 2001; 167: 132–139.PubMedGoogle Scholar
  95. 95.
    Zuberek K, Ling V, Wu P et al. Comparable in vivo efficacy of CD28/B7, ICOS/GL50, and ICOS/GL50B costimulatory pathways in murine tumor models: IFNgamma-dependent enhancement of CTL priming, effector functions, and tumor specific memory CTL. Cell Immunol 2003; 225: 53–63.PubMedCrossRefGoogle Scholar
  96. 96.
    Ara G, Baher A, Storm N et al. Potent activity of soluble B7RP-1-Fc in therapy of murine tumors in syngeneic hosts. Int J Cancer 2003; 103: 501–507.PubMedCrossRefGoogle Scholar
  97. 97.
    Nishimura H, Nose M, Hiai H et al. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 1999; 11: 141–151.PubMedCrossRefGoogle Scholar
  98. 98.
    Dong H, Strome SE, Salomao DR et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8: 793–800.PubMedGoogle Scholar
  99. 99.
    Iwai Y, Ishida M, Tanaka Y et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 2002; 99: 12293–12297.PubMedCrossRefGoogle Scholar
  100. 100.
    Strome SE, Dong H, Tamura H et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res 2003; 63: 6501–6505.PubMedGoogle Scholar
  101. 101.
    Hirano F, Kaneko K, Tamura H et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005; 65: 1089–1096.PubMedGoogle Scholar
  102. 102.
    Blank C, Brown I, Peterson AC et al. PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 2004; 64: 1140–1145.PubMedCrossRefGoogle Scholar
  103. 103.
    Curiel TJ, Wei S, Dong H et al. Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 2003; 9: 562–567.PubMedCrossRefGoogle Scholar
  104. 104.
    Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683–765.PubMedCrossRefGoogle Scholar
  105. 105.
    Radhakrishnan S, Nguyen LT, Ciric B et al. Immunotherapeutic potential of B7-DC (PD-L2) cross-linking antibody in conferring antitumor immunity. Cancer Res 2004; 64: 4965–4972.Google Scholar
  106. 106.
    Brown JA, Dorfman DM, Ma FR et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 2003; 170: 1257–1266.PubMedGoogle Scholar
  107. 107.
    Wintterle S, Schreiner B, Mitsdoerffer M et al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res 2003; 63: 7462–7467.PubMedGoogle Scholar
  108. 108.
    Ohigashi Y, Sho M, Yamada Y et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res 2005; 11: 2947–2953.PubMedCrossRefGoogle Scholar
  109. 109.
    Thompson RH, Gillett MD, Cheville JC et al. Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A 2004; 101: 17174–17179.PubMedCrossRefGoogle Scholar
  110. 110.
    Rosenwald A, Wright G, Leroy K et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003; 198: 851–862.PubMedCrossRefGoogle Scholar
  111. 111.
    Watts TH. TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 2005; 23: 23–68.PubMedCrossRefGoogle Scholar
  112. 112.
    van Lier RA, Borst J, Vroom TM et al. Tissue distribution and biochemical and functional properties of Tp55 (CD27), a novel T cell differentiation antigen. J Immunol 1987; 139: 1589–1596.Google Scholar
  113. 113.
    Bowman MR, Crimmins MA, Yetz-Aldape J et al. The cloning of CD70 and its identification as the ligand for CD27. J Immunol 1994; 152: 1756–1761.PubMedGoogle Scholar
  114. 114.
    Lens SM, de Jong R, Hooibrink B et al. Phenotype and function of human B cells expressing CD70 (CD27 ligand). Eur J Immunol 1996; 26: 2964–2971.PubMedCrossRefGoogle Scholar
  115. 115.
    Oshima H, Nakano H, Nohara C et al. Characterization of murine CD70 by molecular cloning and mAb. Int Immunol 1998; 10: 517–526.PubMedCrossRefGoogle Scholar
  116. 116.
    Wherry EJ, Teichgraber V, Becker TC et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003; 4: 225–234.PubMedCrossRefGoogle Scholar
  117. 117.
    Hendriks J, Gravestein LA, Tesselaar K et al. CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 2000; 1: 433–440.PubMedCrossRefGoogle Scholar
  118. 118.
    Arens R, Tesselaar K, Baars PA et al. Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFNgamma-mediated B cell depletion. Immunity 2001; 15: 801–812.PubMedCrossRefGoogle Scholar
  119. 119.
    Tesselaar K, Arens R, van Schijndel GM et al. Lethal T cell immunodeficiency induced by chronic costimulation via CD27-CD70 interactions. Nat Immunol 2003; 4: 49–54.PubMedCrossRefGoogle Scholar
  120. 120.
    Arens R, Schepers K, Nolte MA et al. Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J Exp Med 2004; 199: 1595–1605.PubMedCrossRefGoogle Scholar
  121. 121.
    Couderc B, Zitvogel L, Douin-Echinard V et al. Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells. Cancer Gene Ther 1998; 5: 163–175.PubMedGoogle Scholar
  122. 122.
    Nieland JD, Graus YF, Dortmans YE et al. CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response. J Immunother 1998; 21: 225–236.PubMedCrossRefGoogle Scholar
  123. 123.
    Lorenz MG, Kantor JA, Schlom J, Hodge JW. Anti-tumor immunity elicited by a recombinant vaccinia virus expressing CD70 (CD27L). Hum Gene Ther 1999; 10: 1095–1103.PubMedCrossRefGoogle Scholar
  124. 124.
    Kelly JM, Darcy PK, Markby JL et al. Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol 2002; 3: 83–90.PubMedCrossRefGoogle Scholar
  125. 125.
    Gramaglia I, Weinberg AD, Lemon M, Croft M. Ox-40 ligand: a potent costimulatory molecule for sustaining primary CD4 T cell responses. J Immunol 1998; 161: 6510–6517.PubMedGoogle Scholar
  126. 126.
    Miura S, Ohtani K, Numata N et al. Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. Mol Cell Biol 1991; 11: 1313–1325.PubMedGoogle Scholar
  127. 127.
    Stuber E, Neurath M, Calderhead D et al. Cross-linking of OX40 ligand, a member of the TNF/NGF cytokine family, induces proliferation and differentiation in murine splenic B cells. Immunity 1995; 2: 507–521.PubMedCrossRefGoogle Scholar
  128. 128.
    Chen AI, McAdam AJ, Buhlmann JE et al. Ox40-ligand has a critical costimulatory role in dendritic cell:T cell interactions. Immunity 1999; 11: 689–698.PubMedCrossRefGoogle Scholar
  129. 129.
    Weinberg AD, Wegmann KW, Funatake C, Whitham RH. Blocking OX-40/OX-40 ligand interaction in vitro and in vivo leads to decreased T cell function and amelioration of experimental allergic encephalomyelitis. J Immunol 1999; 162: 1818–1826.PubMedGoogle Scholar
  130. 130.
    Blazar BR, Sharpe AH, Chen AI et al. Ligation of OX40 (CD134) regulates graft-versus-host disease (GVHD) and graft rejection in allogeneic bone marrow transplant recipients. Blood 2003; 101: 3741–3748.PubMedCrossRefGoogle Scholar
  131. 131.
    Takeda I, Ine S, Killeen N et al. Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. J Immunol 2004; 172: 3580–3589.PubMedGoogle Scholar
  132. 132.
    Bansal-Pakala P, Jember AG, Croft M. Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nat Med 2001; 7: 907–912.PubMedCrossRefGoogle Scholar
  133. 133.
    Gerloni M, Xiong S, Mukerjee S et al. Functional cooperation between T helper cell determinants. Proc Natl Acad Sci U S A 2000; 97: 13269–13274.PubMedCrossRefGoogle Scholar
  134. 134.
    Weinberg AD, Rivera MM, Prell R et al. Engagement of the OX-40 receptor in vivo enhances antitumor immunity. J Immunol 2000; 164: 2160–2169.PubMedGoogle Scholar
  135. 135.
    Kjaergaard J, Tanaka J, Kim JA et al. Therapeutic efficacy of OX-40 receptor antibody depends on tumor immunogenicity and anatomic site of tumor growth. Cancer Res 2000; 60: 5514–5521.PubMedGoogle Scholar
  136. 136.
    Kjaergaard J, Peng L, Cohen PA et al. Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor. J Immunol 2001; 167: 6669–6677.PubMedGoogle Scholar
  137. 137.
    Pan PY, Zang Y, Weber K et al. OX40 ligation enhances primary and memory cytotoxic T lymphocyte responses in an immunotherapy for hepatic colon metastases. Mol Ther 2002; 6: 528–536.PubMedCrossRefGoogle Scholar
  138. 138.
    Morris A, Vetto JT, Ramstad T et al. Induction of anti-mammary cancer immunity by engaging the OX-40 receptor in vivo. Breast Cancer Res Treat 2001; 67: 71–80.PubMedCrossRefGoogle Scholar
  139. 139.
    Gri G, Gallo E, Di Carlo E et al. OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response. J Immunol 2003; 170: 99–106.PubMedGoogle Scholar
  140. 140.
    Kwon BS, Weissman SM. cDNA sequences of two inducible T-cell genes. Proc Natl Acad Sci U S A 1989; 86: 1963–1967.PubMedCrossRefGoogle Scholar
  141. 141.
    Wilcox RA, Tamada K, Strome SE, Chen L. Signaling through NK cell-associated CD137 promotes both helper function for CD8+ cytolytic T cells and responsiveness to IL-2 but not cytolytic activity. J Immunol 2002; 169: 4230–4236.PubMedGoogle Scholar
  142. 142.
    Wilcox RA, Chapoval AI, Gorski KS et al. Cutting edge: Expression of functional CD137 receptor by dendritic cells. J Immunol 2002; 168: 4262–4267.PubMedGoogle Scholar
  143. 143.
    Goodwin RG, Din WS, Davis-Smith T et al. Molecular cloning of a ligand for the inducible T cell gene 4–1BB: a member of an emerging family of cytokines with homology to tumor necrosis factor. Eur J Immunol 1993; 23: 2631–2641.PubMedCrossRefGoogle Scholar
  144. 144.
    Takahashi C, Mittler RS, Vella AT. Cutting edge: 4–1BB is a bona fide CD8 T cell survival signal. J Immunol 1999; 162: 5037–5040.PubMedGoogle Scholar
  145. 145.
    Bukczynski J, Wen T, Ellefsen K et al. Costimulatory ligand 4–1BBL (CD137L) as an efficient adjuvant for human antiviral cytotoxic T cell responses. Proc Natl Acad Sci U S A 2004; 101: 1291–1296.PubMedCrossRefGoogle Scholar
  146. 146.
    Wilcox RA, Tamada K, Flies DB et al. Ligation of CD137 receptor prevents and reverses established anergy of CD8+ cytolytic T lymphocytes in vivo. Blood 2004; 103: 177–184.PubMedCrossRefGoogle Scholar
  147. 147.
    Bukczynski J, Wen T, Watts TH. Costimulation of human CD28- T cells by 4–1BB ligand. Eur J Immunol 2003; 33: 446–454.PubMedCrossRefGoogle Scholar
  148. 148.
    Azuma M, Phillips JH, Lanier LL. CD28- T lymphocytes. Antigenic and functional properties. J Immunol 1993; 150: 1147–1159.PubMedGoogle Scholar
  149. 149.
    Schmidt D, Goronzy JJ, Weyand CM. CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity. J Clin Invest 1996; 97: 2027–2037.PubMedGoogle Scholar
  150. 150.
    Sze DM, Giesajtis G, Brown RD et al. Clonal cytotoxic T cells are expanded in myeloma and reside in the CD8(+)CD57(+)CD28(-) compartment. Blood 2001; 98: 2817–2827.PubMedCrossRefGoogle Scholar
  151. 151.
    Myers L, Takahashi C, Mittler RS et al. Effector CD8 T cells possess suppressor function after 4–1BB and Toll-like receptor triggering. Proc Natl Acad Sci U S A 2003; 100: 5348–5353.PubMedCrossRefGoogle Scholar
  152. 152.
    Sun Y, Lin X, Chen HM et al. Administration of agonistic anti-4–1BB monoclonal antibody leads to the amelioration of experimental autoimmune encephalomyelitis. J Immunol 2002; 168: 1457–1465.PubMedGoogle Scholar
  153. 153.
    Hellstrom KE, Hellstrom I. Therapeutic vaccination with tumor cells that engage CD137. J Mol Med 2003; 81: 71–86.PubMedGoogle Scholar
  154. 154.
    Melero I, Shuford WW, Newby SA et al. Monoclonal antibodies against the 4–1BB T-cell activation molecule eradicate established tumors. Nat Med 1997; 3: 682–685.PubMedCrossRefGoogle Scholar
  155. 155.
    Diehl L, van Mierlo GJ, den Boer AT et al. In vivo triggering through 4–1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway. J Immunol 2002; 168: 3755–3762.PubMedGoogle Scholar
  156. 156.
    Taraban VY, Rowley TF, O’Brien L et al. Expression and costimulatory effects of the TNF receptor superfamily members CD134 (OX40) and CD137 (4–1BB), and their role in the generation of anti-tumor immune responses. Eur J Immunol 2002; 32: 3617–3627.PubMedCrossRefGoogle Scholar
  157. 157.
    Martinet O, Ermekova V, Qiao JQ et al. Immunomodulatory gene therapy with interleukin 12 and 4–1BB ligand: long- term remission of liver metastases in a mouse model. J Natl Cancer Inst 2000; 92: 931–936.PubMedCrossRefGoogle Scholar
  158. 158.
    Ye Z, Hellstrom I, Hayden-Ledbetter M et al. Gene therapy for cancer using single-chain Fv fragments specific for 4–1BB. Nat Med 2002; 8: 343–348.PubMedCrossRefGoogle Scholar
  159. 159.
    Melero I, Johnston JV, Shufford WW et al. NK1.1 cells express 4–1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4–1BB monoclonal antibodies. Cell Immunol 1998; 190: 167–172.PubMedCrossRefGoogle Scholar
  160. 160.
    Pan PY, Gu P, Li Q et al. Regulation of dendritic cell function by NK cells: mechanisms underlying the synergism in the combination therapy of IL-12 and 4–1BB activation. J Immunol 2004; 172: 4779–4789.PubMedGoogle Scholar
  161. 161.
    Wilcox RA, Flies DB, Zhu G et al. Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest 2002; 109: 651–659.PubMedCrossRefGoogle Scholar
  162. 162.
    Bertram EM, Lau P, Watts TH. Temporal segregation of 4–1BB versus CD28-mediated costimulation: 4–1BB ligand influences T cell numbers late in the primary response and regulates the size of the T cell memory response following influenza infection. J Immunol 2002; 168: 3777–3785.PubMedGoogle Scholar
  163. 163.
    Melero I, Bach N, Hellstrom KE et al. Amplification of tumor immunity by gene transfer of the co-stimulatory 4–1BB ligand: synergy with the CD28 co-stimulatory pathway. Eur J Immunol 1998; 28: 1116–1121.PubMedCrossRefGoogle Scholar
  164. 164.
    Guinn BA, DeBenedette MA, Watts TH, Berinstein NL. 4–1BBL cooperates with B7–1 and B7–2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine. J Immunol 1999; 162: 5003–5010.PubMedGoogle Scholar
  165. 165.
    Shuford WW, Klussman K, Tritchler DD et al. 4–1BB costimulatory signals preferentially induce CD8+ T cell proliferation and lead to the amplification in vivo of cytotoxic T cell responses. J Exp Med 1997; 186: 47–55.PubMedCrossRefGoogle Scholar
  166. 166.
    Montgomery RI, Warner MS, Lum BJ, Spear PG. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Cell 1996; 87: 427–436.PubMedCrossRefGoogle Scholar
  167. 167.
    Mauri DN, Ebner R, Montgomery RI et al. LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are ligands for herpesvirus entry mediator. Immunity 1998; 8: 21–30.PubMedCrossRefGoogle Scholar
  168. 168.
    Sedy JR, Gavrieli M, Potter KG et al. B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol 2005; 6: 90–98.PubMedCrossRefGoogle Scholar
  169. 169.
    Gonzalez LC, Loyet KM, Calemine-Fenaux J et al. A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Proc Natl Acad Sci U S A 2005; 102: 1116–1121.PubMedCrossRefGoogle Scholar
  170. 170.
    Granger SW, Rickert S. LIGHT-HVEM signaling and the regulation of T cell-mediated immunity. Cytokine Growth Factor Rev 2003; 14: 289–296.PubMedCrossRefGoogle Scholar
  171. 171.
    Harrop JA, McDonnell PC, Brigham-Burke M et al. Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth. J Biol Chem 1998; 273: 27548–27556.PubMedCrossRefGoogle Scholar
  172. 172.
    Tamada K, Shimozaki K, Chapoval AI et al. LIGHT, a TNF-like molecule, costimulates T cell proliferation and is required for dendritic cell-mediated allogeneic T cell response. J Immunol 2000; 164: 4105–4110.PubMedGoogle Scholar
  173. 173.
    Tamada K, Shimozaki K, Chapoval AI et al. Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway. Nat Med 2000; 6: 283–289.PubMedCrossRefGoogle Scholar
  174. 174.
    Morel Y, Truneh A, Sweet RW et al. The TNF superfamily members LIGHT and CD154 (CD40 ligand) costimulate induction of dendritic cell maturation and elicit specific CTL activity. J Immunol 2001; 167: 2479–2486.PubMedGoogle Scholar
  175. 175.
    Shaikh RB, Santee S, Granger SW et al. Constitutive expression of LIGHT on T cells leads to lymphocyte activation, inflammation, and tissue destruction. J Immunol 2001; 167: 6330–6337.PubMedGoogle Scholar
  176. 176.
    Scheu S, Alferink J, Potzel T et al. Targeted disruption of LIGHT causes defects in costimulatory T cell activation and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis. J Exp Med 2002; 195: 1613–1624.PubMedCrossRefGoogle Scholar
  177. 177.
    Watanabe N, Gavrieli M, Sedy JR et al. BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol 2003; 4: 670–679.PubMedCrossRefGoogle Scholar
  178. 178.
    Han P, Goularte OD, Rufner K et al. An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. J Immunol 2004; 172: 5931–5939.PubMedGoogle Scholar
  179. 179.
    Zhai Y, Guo R, Hsu TL et al. LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. J Clin Invest 1998; 102: 1142–1151.PubMedGoogle Scholar
  180. 180.
    Rooney IA, Butrovich KD, Glass AA et al. The lymphotoxin-beta receptor is necessary and sufficient for LIGHT-mediated apoptosis of tumor cells. J Biol Chem 2000; 275: 14307–14315.PubMedCrossRefGoogle Scholar
  181. 181.
    Yu P, Lee Y, Liu W et al. Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 2004; 5: 141–149.PubMedCrossRefGoogle Scholar
  182. 182.
    Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998; 16: 111–135.PubMedCrossRefGoogle Scholar
  183. 183.
    Boumpas DT, Furie R, Manzi S et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum 2003; 48: 719–727.PubMedCrossRefGoogle Scholar
  184. 184.
    Sidiropoulos PI, Boumpas DT. Lessons learned from anti-CD40L treatment in systemic lupus erythematosus patients. Lupus 2004; 13: 391–397.PubMedCrossRefGoogle Scholar
  185. 185.
    Kluin-Nelemans HC, Beverstock GC, Mollevanger P et al. Proliferation and cytogenetic analysis of hairy cell leukemia upon stimulation via the CD40 antigen. Blood 1994; 84: 3134–3141.PubMedGoogle Scholar
  186. 186.
    Funakoshi S, Longo DL, Beckwith M et al. Inhibition of human B-cell lymphoma growth by CD40 stimulation. Blood 1994; 83: 2787–2794.PubMedGoogle Scholar
  187. 187.
    Ghamande S, Hylander BL, Oflazoglu E et al. Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin. Cancer Res 2001; 61: 7556–7562.PubMedGoogle Scholar
  188. 188.
    Hirano A, Longo DL, Taub DD et al. Inhibition of human breast carcinoma growth by a soluble recombinant human CD40 ligand. Blood 1999; 93: 2999–3007.PubMedGoogle Scholar
  189. 189.
    Posner MR, Cavacini LA, Upton MP et al. Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines. Clin Cancer Res 1999; 5: 2261–2270.PubMedGoogle Scholar
  190. 190.
    Yamada M, Shiroko T, Kawaguchi Y et al. CD40-CD40 ligand (CD154) engagement is required but not sufficient for modulating MHC class I, ICAM-1 and Fas expression and proliferation of human non-small cell lung tumors. Int J Cancer 2001; 92: 589–599.PubMedCrossRefGoogle Scholar
  191. 191.
    Mackey MF, Gunn JR, Ting PP et al. Protective immunity induced by tumor vaccines requires interaction between CD40 and its ligand, CD154. Cancer Res 1997; 57: 2569–2574.PubMedGoogle Scholar
  192. 192.
    Noguchi M, Imaizumi K, Kawabe T et al. Induction of antitumor immunity by transduction of CD40 ligand gene and interferon-gamma gene into lung cancer. Cancer Gene Ther 2001; 8: 421–429.PubMedCrossRefGoogle Scholar
  193. 193.
    Grangeon C, Cormary C, Douin-Echinard V et al. In vivo induction of antitumor immunity and protection against tumor growth by injection of CD154-expressing tumor cells. Cancer Gene Ther 2002; 9: 282–288.PubMedCrossRefGoogle Scholar
  194. 194.
    Grossmann ME, Brown MP, Brenner MK. Antitumor responses induced by transgenic expression of CD40 ligand. Hum Gene Ther 1997; 8: 1935–1943.PubMedGoogle Scholar
  195. 195.
    Liu Y, Zhang X, Zhang W et al. Adenovirus-mediated CD40 ligand gene-engineered dendritic cells elicit enhanced CD8(+) cytotoxic T-cell activation and antitumor immunity. Cancer Gene Ther 2002; 9: 202–208.PubMedCrossRefGoogle Scholar
  196. 196.
    Sun Y, Peng D, Lecanda J et al. In vivo gene transfer of CD40 ligand into colon cancer cells induces local production of cytokines and chemokines, tumor eradication and protective antitumor immunity. Gene Ther 2000; 7: 1467–1476.PubMedCrossRefGoogle Scholar
  197. 197.
    Xiang R, Primus FJ, Ruehlmann JM et al. A dual-function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell-mediated protective immunity against colon cancer in carcinoembryonic antigen-transgenic mice. J Immunol 2001; 167: 4560–4565.PubMedGoogle Scholar
  198. 198.
    Chiodoni C, Paglia P, Stoppacciaro A et al. Dendritic cells infiltrating tumors cotransduced with granulocyte/macrophage colony-stimulating factor (GM-CSF) and CD40 ligand genes take up and present endogenous tumor-associated antigens, and prime naive mice for a cytotoxic T lymphocyte response. J Exp Med 1999; 190: 125–133.PubMedCrossRefGoogle Scholar
  199. 199.
    Peter I, Nawrath M, Kamarashev J et al. Immunotherapy for murine K1735 melanoma: combinatorial use of recombinant adenovirus expressing CD40L and other immunomodulators. Cancer Gene Ther 2002; 9: 597–605.PubMedCrossRefGoogle Scholar
  200. 200.
    Ito D, Ogasawara K, Iwabuchi K et al. Induction of CTL responses by simultaneous administration of liposomal peptide vaccine with anti-CD40 and anti-CTLA-4 mAb. J Immunol 2000; 164: 1230–1235.PubMedGoogle Scholar
  201. 201.
    Schultze JL, Anderson KC, Gilleece MH et al. A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2. Br J Haematol 2001; 113: 455–460.PubMedCrossRefGoogle Scholar
  202. 202.
    Hayashi T, Treon SP, Hideshima T et al. Recombinant humanized anti-CD40 monoclonal antibody triggers autologous antibody-dependent cell-mediated cytotoxicity against multiple myeloma cells. Br J Haematol 2003; 121: 592–596.PubMedCrossRefGoogle Scholar
  203. 203.
    Law CL, Gordon KA, Collier J et al. Preclinical antilymphoma activity of a humanized anti-CD40 monoclonal antibody, SGN-40. Cancer Res 2005; 65: 8331–8338.PubMedCrossRefGoogle Scholar
  204. 204.
    Nocentini G, Giunchi L, Ronchetti S et al. A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc Natl Acad Sci U S A 1997; 94: 6216–6221.PubMedCrossRefGoogle Scholar
  205. 205.
    Gurney AL, Marsters SA, Huang RM et al. Identification of a new member of the tumor necrosis factor family and its receptor, a human ortholog of mouse GITR. Curr Biol 1999; 9: 215–218.PubMedCrossRefGoogle Scholar
  206. 206.
    Kohm AP, Williams JS, Miller SD. Cutting edge: ligation of the glucocorticoid-induced TNF receptor enhances autoreactive CD4+ T cell activation and experimental autoimmune encephalomyelitis. J Immunol 2004; 172: 4686–4690.PubMedGoogle Scholar
  207. 207.
    Kanamaru F, Youngnak P, Hashiguchi M et al. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J Immunol 2004; 172: 7306–7314.Google Scholar
  208. 208.
    Ronchetti S, Zollo O, Bruscoli S et al. GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations. Eur J Immunol 2004; 34: 613–622.PubMedCrossRefGoogle Scholar
  209. 209.
    Tone M, Tone Y, Adams E et al. Mouse glucocorticoid-induced tumor necrosis factor receptor ligand is costimulatory for T cells. Proc Natl Acad Sci U S A 2003; 100: 15059–15064.PubMedCrossRefGoogle Scholar
  210. 210.
    Stephens GL, McHugh RS, Whitters MJ et al. Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J Immunol 2004; 173: 5008–5020.PubMedGoogle Scholar
  211. 211.
    Shimizu J, Yamazaki S, Takahashi T et al. Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 2002; 3: 135–142.PubMedCrossRefGoogle Scholar
  212. 212.
    McHugh RS, Whitters MJ, Piccirillo CA et al. CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002; 16: 311–323.PubMedCrossRefGoogle Scholar
  213. 213.
    Muriglan SJ, Ramirez-Montagut T, Alpdogan O et al. GITR activation induces an opposite effect on alloreactive CD4(+) and CD8(+) T cells in graft-versus-host disease. J Exp Med 2004; 200: 149–157.PubMedCrossRefGoogle Scholar
  214. 214.
    Suri A, Shimizu J, Katz JD et al. Regulation of autoimmune diabetes by non-islet-specific T cells – a role for the glucocorticoid-induced TNF receptor. Eur J Immunol 2004; 34: 447–454.PubMedCrossRefGoogle Scholar
  215. 215.
    Valzasina B, Guiducci C, Dislich H et al. Triggering of OX40 (CD134) on CD4(+)CD25+ T cells blocks their inhibitory activity: a novel regulatory role for OX40 and its comparison with GITR. Blood 2005; 105: 2845–2851.PubMedCrossRefGoogle Scholar
  216. 216.
    Kirkwood J. Cancer immunotherapy: the interferon-alpha experience. Semin Oncol 2002; 29: 18–26.PubMedCrossRefGoogle Scholar
  217. 217.
    Atkins MB. Interleukin-2: clinical applications. Semin Oncol 2002; 29: 12–17.PubMedCrossRefGoogle Scholar
  218. 218.
    Welte K, Gabrilove J, Bronchud MH et al. Filgrastim (r-metHuG-CSF): the first 10 years. Blood 1996; 88: 1907–1929.PubMedGoogle Scholar
  219. 219.
    Armitage JO. Emerging applications of recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1998; 92: 4491–4508.PubMedGoogle Scholar
  220. 220.
    Coscia M, Biragyn A. Cancer immunotherapy with chemoattractant peptides. Semin Cancer Biol 2004; 14: 209–218.PubMedCrossRefGoogle Scholar
  221. 221.
    Zlotnik A. Chemokines in neoplastic progression. Semin Cancer Biol 2004; 14: 181–185.PubMedCrossRefGoogle Scholar
  222. 222.
    Conti I, Rollins BJ. CCL2 (monocyte chemoattractant protein-1) and cancer. Semin Cancer Biol 2004; 14: 149–154.PubMedCrossRefGoogle Scholar
  223. 223.
    Carswell EA, Old LJ, Kassel RL et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975; 72: 3666–3670.PubMedCrossRefGoogle Scholar
  224. 224.
    Mocellin S, Rossi CR, Pilati P, Nitti D. Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev 2005; 16: 35–53.PubMedCrossRefGoogle Scholar
  225. 225.
    Bemelmans MH, van Tits LJ, Buurman WA. Tumor necrosis factor: function, release and clearance. Crit Rev Immunol 1996; 16: 1–11.PubMedGoogle Scholar
  226. 226.
    Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 2003; 3: 745–756.PubMedCrossRefGoogle Scholar
  227. 227.
    Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science 2002; 296: 1634–1635.PubMedCrossRefGoogle Scholar
  228. 228.
    Herrmann F, Bambach T, Bonifer R et al. The suppressive effects of recombinant human tumor necrosis factor-alpha on normal and malignant myelopoiesis: synergism with interferon-gamma. Int J Cell Cloning 1988; 6: 241–261.PubMedGoogle Scholar
  229. 229.
    MacPherson GG, North RJ. Endotoxin-mediated necrosis and regression of established tumours in the mouse. A correlative study of quantitative changes in blood flow and ultrastructural morphology. Cancer Immunol Immunother 1986; 21: 209–216.PubMedCrossRefGoogle Scholar
  230. 230.
    Palladino MA, Jr., Shalaby MR, Kramer SM et al. Characterization of the antitumor activities of human tumor necrosis factor-alpha and the comparison with other cytokines: induction of tumor-specific immunity. J Immunol 1987; 138: 4023–4032.PubMedGoogle Scholar
  231. 231.
    Vujanovic NL. Role of TNF family ligands in antitumor activity of natural killer cells. Int Rev Immunol 2001; 20: 415–437.PubMedGoogle Scholar
  232. 232.
    Mocellin S, Provenzano M, Lise M et al. Increased TIA-1 gene expression in the tumor microenvironment after locoregional administration of tumor necrosis factor-alpha to patients with soft tissue limb sarcoma. Int J Cancer 2003; 107: 317–322.PubMedCrossRefGoogle Scholar
  233. 233.
    Grunhagen DJ, Brunstein F, ten Hagen TL et al. TNF-based isolated limb perfusion: a decade of experience with antivascular therapy in the management of locally advanced extremity soft tissue sarcomas. Cancer Treat Res 2004; 120: 65–79.PubMedGoogle Scholar
  234. 234.
    Grunhagen DJ, Brunstein F, Graveland WJ et al. One hundred consecutive isolated limb perfusions with TNF-alpha and melphalan in melanoma patients with multiple in-transit metastases. Ann Surg 2004; 240: 939–947; discussion 947–938.Google Scholar
  235. 235.
    Di Filippo F, Cavaliere F, Garinei R et al. TNFa-based isolated hyperthermic limb perfusion (HILP) in the treatment of limb recurrent melanoma: update 16 years after its first clinical application. J Chemother 2004; 16 Suppl 5: 62–65.Google Scholar
  236. 236.
    Grover A, Alexander HR, Jr. The past decade of experience with isolated hepatic perfusion. Oncologist 2004; 9: 653–664.PubMedCrossRefGoogle Scholar
  237. 237.
    Lejeune FJ. Clinical use of TNF revisited: improving penetration of anti-cancer agents by increasing vascular permeability. J Clin Invest 2002; 110: 433–435.PubMedCrossRefGoogle Scholar
  238. 238.
    Rossi CR, Foletto M, Pilati P et al. Isolated limb perfusion in locally advanced cutaneous melanoma. Semin Oncol 2002; 29: 400–409.PubMedCrossRefGoogle Scholar
  239. 239.
    Rossi CR, Mocellin S, Pilati P et al. TNFalpha-based isolated perfusion for limb-threatening soft tissue sarcomas: state of the art and future trends. J Immunother 2003; 26: 291–300.PubMedCrossRefGoogle Scholar
  240. 240.
    Kahn JO, Kaplan LD, Volberding PA et al. Intralesional recombinant tumor necrosis factor-alpha for AIDS-associated Kaposi’s sarcoma: a randomized, double-blind trial. J Acquir Immune Defic Syndr 1989; 2: 217–223.PubMedGoogle Scholar
  241. 241.
    Senzer N, Mani S, Rosemurgy A et al. TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors. J Clin Oncol 2004; 22: 592–601.PubMedCrossRefGoogle Scholar
  242. 242.
    Curnis F, Sacchi A, Borgna L et al. Enhancement of tumor necrosis factor alpha antitumor immunotherapeutic properties by targeted delivery to aminopeptidase N (CD13). Nat Biotechnol 2000; 18: 1185–1190.PubMedCrossRefGoogle Scholar
  243. 243.
    Dranoff G, Jaffee E, Lazenby A et al. Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proceedings of the National Academy of Sciences of the United States of America 1993; 90: 3539–3543.Google Scholar
  244. 244.
    Kielian T, Nagai E, Ikubo A et al. Granulocyte/macrophage-colony-stimulating factor released by adenovirally transduced CT26 cells leads to the local expression of macrophage inflammatory protein 1alpha and accumulation of dendritic cells at vaccination sites in vivo. Cancer Immunol Immunother 1999; 48: 123–131.PubMedCrossRefGoogle Scholar
  245. 245.
    Shinohara H, Yano S, Bucana CD, Fidler IJ. Induction of chemokine secretion and enhancement of contact-dependent macrophage cytotoxicity by engineered expression of granulocyte-macrophage colony-stimulating factor in human colon cancer cells. J Immunol 2000; 164: 2728–2737.PubMedGoogle Scholar
  246. 246.
    Sanda MG, Ayyagari SR, Jaffee EM et al. Demonstration of a rational strategy for human prostate cancer gene therapy. Journal of Urology 1994; 151: 622–628.PubMedGoogle Scholar
  247. 247.
    Dunussi-Joannopoulos K, Dranoff G, Weinstein HJ et al. Gene immunotherapy in murine acute myeloid leukemia: granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines. Blood 1998; 91: 222–230.PubMedGoogle Scholar
  248. 248.
    Levitsky HI, Montgomery J, Ahmadzadeh M et al. Immunization with granulocyte-macrophage colony-stimulating factor-transduced, but not B7–1-transduced, lymphoma cells primes idiotype-specific T cells and generates potent systemic antitumor immunity. J Immunol 1996; 156: 3858–3865.PubMedGoogle Scholar
  249. 249.
    Spitler LE, Grossbard ML, Ernstoff MS et al. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol 2000; 18: 1614–1621.Google Scholar
  250. 250.
    Chang DH, Dhodapkar MV. Dendritic cells and immunotherapy for cancer. Int J Hematol 2003; 77: 439–443.PubMedCrossRefGoogle Scholar
  251. 251.
    Buchler T, Michalek J, Kovarova L et al. Dendritic cell-based immunotherapy for the treatment of hematological malignancies. Hematology 2003; 8: 97–104.PubMedCrossRefGoogle Scholar
  252. 252.
    Chang DZ, Lomazow W, Joy Somberg C et al. Granulocyte-macrophage colony stimulating factor: an adjuvant for cancer vaccines. Hematology 2004; 9: 207–215.PubMedCrossRefGoogle Scholar
  253. 253.
    Schaed SG, Klimek VM, Panageas KS et al. T-cell responses against tyrosinase 368–376(370D) peptide in HLA(*)A0201(+) melanoma patients: randomized trial comparing incomplete Freund’s adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants. Clin Cancer Res 2002; 8: 967–972.PubMedGoogle Scholar
  254. 254.
    Jager E, Ringhoffer M, Dienes HP et al. Granulocyte-macrophage-colony-stimulating factor enhances immune responses to melanoma-associated peptides in vivo. Int J Cancer 1996; 67: 54–62.PubMedCrossRefGoogle Scholar
  255. 255.
    Scheibenbogen C, Schmittel A, Keilholz U et al. Phase 2 trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. J Immunother 2000; 23: 275–281.PubMedCrossRefGoogle Scholar
  256. 256.
    Scheibenbogen C, Schadendorf D, Bechrakis NE et al. Effects of granulocyte-macrophage colony-stimulating factor and foreign helper protein as immunologic adjuvants on the T-cell response to vaccination with tyrosinase peptides. Int J Cancer 2003; 104: 188–194.PubMedCrossRefGoogle Scholar
  257. 257.
    Weber J, Sondak VK, Scotland R et al. Granulocyte-macrophage-colony-stimulating factor added to a multipeptide vaccine for resected Stage II melanoma. Cancer 2003; 97: 186–200.PubMedCrossRefGoogle Scholar
  258. 258.
    Disis ML, Grabstein KH, Sleath PR, Cheever MA. Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. Clin Cancer Res 1999; 5: 1289–1297.PubMedGoogle Scholar
  259. 259.
    von Mehren M, Arlen P, Gulley J et al. The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clin Cancer Res 2001; 7: 1181–1191.Google Scholar
  260. 260.
    Ullenhag GJ, Frodin JE, Mosolits S et al. Immunization of colorectal carcinoma patients with a recombinant canarypox virus expressing the tumor antigen Ep-CAM/KSA (ALVAC-KSA) and granulocyte macrophage colony- stimulating factor induced a tumor-specific cellular immune response. Clin Cancer Res 2003; 9: 2447–2456.PubMedGoogle Scholar
  261. 261.
    Kwak LW, Young HA, Pennington RW, Weeks SD. Vaccination with syngeneic, lymphoma-derived immunoglobulin idiotype combined with granulocyte/macrophage colony-stimulating factor primes mice for a protective T-cell response. Proc Natl Acad Sci U S A 1996; 93: 10972–10977.Google Scholar
  262. 262.
    Timmerman JM, Levy R. Linkage of foreign carrier protein to a self-tumor antigen enhances the immunogenicity of a pulsed dendritic cell vaccine. J Immunol 2000; 164: 4797–4803.PubMedGoogle Scholar
  263. 263.
    Pasquini S, Peralta S, Missiaglia E et al. Prime-boost vaccines encoding an intracellular idiotype/GM-CSF fusion protein induce protective cell-mediated immunity in murine pre-B cell leukemia. Gene Ther 2002; 9: 503–510.PubMedCrossRefGoogle Scholar
  264. 264.
    Ellem KA, O’Rourke MG, Johnson GR et al. A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy. Cancer Immunol Immunother 1997; 44: 10–20.PubMedCrossRefGoogle Scholar
  265. 265.
    Dranoff G, Soiffer R, Lynch T et al. A phase I study of vaccination with autologous, irradiated melanoma cells engineered to secrete human granulocyte-macrophage colony stimulating factor. Hum Gene Ther 1997; 8: 111–123.PubMedGoogle Scholar
  266. 266.
    Soiffer R, Lynch T, Mihm M et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci U S A 1998; 95: 13141–13146.Google Scholar
  267. 267.
    Chang AE, Li Q, Bishop DK et al. Immunogenetic therapy of human melanoma utilizing autologous tumor cells transduced to secrete granulocyte-macrophage colony-stimulating factor. Hum Gene Ther 2000; 11: 839–850.PubMedCrossRefGoogle Scholar
  268. 268.
    Soiffer R, Hodi FS, Haluska F et al. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J Clin Oncol 2003; 21: 3343–3350.PubMedCrossRefGoogle Scholar
  269. 269.
    Simons JW. Bioactivity of human GM-CSF gene therapy in metastatic renal cell carcinoma and prostate cancer. Hinyokika Kiyo 1997; 43: 821–822.PubMedGoogle Scholar
  270. 270.
    Simons JW, Mikhak B, Chang JF et al. Induction of immunity to prostate cancer antigens: results of a clinical trial of vaccination with irradiated autologous prostate tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer. Cancer Res 1999; 59: 5160–5168.PubMedGoogle Scholar
  271. 271.
    Jaffee EM, Dranoff G, Cohen LK et al. High efficiency gene transfer into primary human tumor explants without cell selection. Cancer Research 1993; 53: 2221–2226.PubMedGoogle Scholar
  272. 272.
    Borrello I, Sotomayor EM, Cooke S, Levitsky HI. A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines. Hum Gene Ther 1999; 10: 1983–1991.PubMedCrossRefGoogle Scholar
  273. 273.
    Qin H, Chatterjee SK. Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. Hum Gene Ther 1996; 7: 1853–1860.PubMedGoogle Scholar
  274. 274.
    Kass E, Parker J, Schlom J, Greiner JW. Comparative studies of the effects of recombinant GM-CSF and GM-CSF administered via a poxvirus to enhance the concentration of antigen- presenting cells in regional lymph nodes. Cytokine 2000; 12: 960–971.PubMedCrossRefGoogle Scholar
  275. 275.
    Bowne WB, Wolchok JD, Hawkins WG et al. Injection of DNA encoding granulocyte-macrophage colony-stimulating factor recruits dendritic cells for immune adjuvant effects. Cytokines Cell Mol Ther 1999; 5: 217–225.PubMedGoogle Scholar
  276. 276.
    Perales MA, Fantuzzi G, Goldberg SM et al. GM-CSF DNA induces specific patterns of cytokines and chemokines in the skin: implications for DNA vaccines. Cytokines Cell Mol Ther 2002; 7: 125–133.PubMedCrossRefGoogle Scholar
  277. 277.
    Bowne WB, Srinivasan R, Wolchok JD et al. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med 1999; 190: 1717–1722.PubMedCrossRefGoogle Scholar
  278. 278.
    Weiss WR, Ishii KJ, Hedstrom RC et al. A plasmid encoding murine granulocyte-macrophage colony-stimulating factor increases protection conferred by a malaria DNA vaccine. J Immunol 1998; 161: 2325–2332.PubMedGoogle Scholar
  279. 279.
    Raviprakash K, Ewing D, Simmons M et al. Needle-free Biojector injection of a dengue virus type 1 DNA vaccine with human immunostimulatory sequences and the GM-CSF gene increases immunogenicity and protection from virus challenge in Aotus monkeys. Virology 2003; 315: 345–352.PubMedCrossRefGoogle Scholar
  280. 280.
    Sakata T, Iwagami S, Tsuruta Y et al. Constitutive expression of interleukin-7 mRNA and production of IL-7 by a cloned murine thymic stromal cell line. J. Leukoc. Biol. 1990; 48: 205–212.Google Scholar
  281. 281.
    Heufler C, Topar G, Grasseger A et al. Interleukin 7 is produced by murine and human keratinocytes. J. Exp. Med. 1993; 178: 1109–1114.Google Scholar
  282. 282.
    Madrigal-Estebas L, McManus R, Byrne B et al. Human small intestinal epithelial cells secrete interleukin-7 and differentially express two different interleukin-7 mRNA Transcripts: implications for extrathymic T-cell differentiation. Hum. Immunol. 1997; 58: 83–90.Google Scholar
  283. 283.
    Fry TJ, Mackall CL. Interleukin-7: from bench to clinic. Blood 2002; 99: 3892–3904.PubMedCrossRefGoogle Scholar
  284. 284.
    Noguchi M, Nakamura Y, Russell SM et al. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor [see comments]. Science 1993; 262: 1877–1880.PubMedCrossRefGoogle Scholar
  285. 285.
    Goodwin RG, Friend D, Ziegler SF et al. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell 1990; 60: 941–951.PubMedCrossRefGoogle Scholar
  286. 286.
    He YW, Malek TR. The structure and function of gamma c-dependent cytokines and receptors: regulation of T lymphocyte development and homeostasis. Crit Rev Immunol 1998; 18: 503–524.PubMedGoogle Scholar
  287. 287.
    Uribe L, Weinberg KI. X-linked SCID and other defects of cytokine pathways. Semin Hematol 1998; 35: 299–309.PubMedGoogle Scholar
  288. 288.
    Asao H, Okuyama C, Kumaki S et al. Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol 2001; 167: 1–5.PubMedGoogle Scholar
  289. 289.
    von Freeden-Jeffry U, Vieira P, Lucian LA et al. Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine. J Exp Med 1995; 181: 1519–1526.CrossRefGoogle Scholar
  290. 290.
    Peschon JJ, Morrissey PJ, Grabstein KH et al. Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice. J Exp Med 1994; 180: 1955–1960.PubMedCrossRefGoogle Scholar
  291. 291.
    Alpdogan O, van den Brink MR. IL-7 and IL-15: therapeutic cytokines for immunodeficiency. Trends Immunol 2005; 26: 56–64.PubMedCrossRefGoogle Scholar
  292. 292.
    Schluns KS, Kieper WC, Jameson SC, Lefrancois L. Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat Immunol 2000; 1: 426–432.PubMedCrossRefGoogle Scholar
  293. 293.
    Kaech SM, Tan JT, Wherry EJ et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 2003; 4: 1191–1198.PubMedCrossRefGoogle Scholar
  294. 294.
    Sempowski GD, Gooding ME, Liao HX et al. T cell receptor excision circle assessment of thymopoiesis in aging mice. Mol Immunol 2002; 38: 841–848.PubMedCrossRefGoogle Scholar
  295. 295.
    Bolotin E, Smogorzewska M, Smith S et al. Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood 1996; 88: 1887–1894.PubMedGoogle Scholar
  296. 296.
    Okamoto Y, Douek DC, McFarland RD, Koup RA. Effects of exogenous interleukin-7 on human thymus function. Blood 2002; 99: 2851–2858.PubMedCrossRefGoogle Scholar
  297. 297.
    Alpdogan O, Muriglan SJ, Eng JM et al. IL-7 enhances peripheral T cell reconstitution after allogeneic hematopoietic stem cell transplantation. J Clin Invest 2003; 112: 1095–1107.PubMedCrossRefGoogle Scholar
  298. 298.
    Abdul-Hai A, Or R, Slavin S et al. Stimulation of immune reconstitution by interleukin-7 after syngeneic bone marrow transplantation in mice. Exp Hematol 1996; 24: 1416–1422.PubMedGoogle Scholar
  299. 299.
    Alpdogan O, Schmaltz C, Muriglan SJ et al. Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease. Blood 2001; 98: 2256–2265.PubMedCrossRefGoogle Scholar
  300. 300.
    Mackall CL, Fry TJ, Bare C et al. IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 2001; 97: 1491–1497.PubMedCrossRefGoogle Scholar
  301. 301.
    Storek J, Gillespy T, 3rd, Lu H et al. Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys. Blood 2003; 101: 4209–4218.PubMedCrossRefGoogle Scholar
  302. 302.
    Kobayashi M, Fitz L, Ryan M et al. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 1989; 170: 827–845.PubMedCrossRefGoogle Scholar
  303. 303.
    Stern AS, Podlaski FJ, Hulmes JD et al. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci U S A 1990; 87: 6808–6812.Google Scholar
  304. 304.
    Oppmann B, Lesley R, Blom B et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 2000; 13: 715–725.PubMedCrossRefGoogle Scholar
  305. 305.
    Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3: 133–146.PubMedCrossRefGoogle Scholar
  306. 306.
    Manetti R, Parronchi P, Giudizi MG et al. Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells. J Exp Med 1993; 177: 1199–1204.PubMedCrossRefGoogle Scholar
  307. 307.
    Manetti R, Gerosa F, Giudizi MG et al. Interleukin 12 induces stable priming for interferon gamma (IFN-gamma) production during differentiation of human T helper (Th) cells and transient IFN-gamma production in established Th2 cell clones. J Exp Med 1994; 179: 1273–1283.PubMedCrossRefGoogle Scholar
  308. 308.
    Perussia B, Chan SH, D’Andrea A et al. Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells. J Immunol 1992; 149: 3495–3502.PubMedGoogle Scholar
  309. 309.
    Bertagnolli MM, Lin BY, Young D, Herrmann SH. IL-12 augments antigen-dependent proliferation of activated T lymphocytes. J Immunol 1992; 149: 3778–3783.PubMedGoogle Scholar
  310. 310.
    Gately MK, Desai BB, Wolitzky AG et al. Regulation of human lymphocyte proliferation by a heterodimeric cytokine, IL-12 (cytotoxic lymphocyte maturation factor). J Immunol 1991; 147: 874–882.PubMedGoogle Scholar
  311. 311.
    Murphy EE, Terres G, Macatonia SE et al. B7 and interleukin 12 cooperate for proliferation and interferon gamma production by mouse T helper clones that are unresponsive to B7 costimulation. J Exp Med 1994; 180: 223–231.PubMedCrossRefGoogle Scholar
  312. 312.
    Noguchi Y, Jungbluth A, Richards EC, Old LJ. Effect of interleukin 12 on tumor induction by 3-methylcholanthrene. Proc Natl Acad Sci U S A 1996; 93: 11798–11801.PubMedCrossRefGoogle Scholar
  313. 313.
    Brunda MJ, Luistro L, Warrier RR et al. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 1993; 178: 1223–1230.PubMedCrossRefGoogle Scholar
  314. 314.
    Cavallo F, Signorelli P, Giovarelli M et al. Antitumor efficacy of adenocarcinoma cells engineered to produce interleukin 12 (IL-12) or other cytokines compared with exogenous IL-12. J Natl Cancer Inst 1997; 89: 1049–1058.PubMedCrossRefGoogle Scholar
  315. 315.
    Noguchi Y, Richards EC, Chen YT, Old LJ. Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma. Proc Natl Acad Sci U S A 1995; 92: 2219–2223.PubMedCrossRefGoogle Scholar
  316. 316.
    Irvine KR, Rao JB, Rosenberg SA, Restifo NP. Cytokine enhancement of DNA immunization leads to effective treatment of established pulmonary metastases. J Immunol 1996; 156: 238–245.PubMedGoogle Scholar
  317. 317.
    Nanni P, Nicoletti G, De Giovanni C et al. Combined allogeneic tumor cell vaccination and systemic interleukin 12 prevents mammary carcinogenesis in HER-2/neu transgenic mice. J Exp Med 2001; 194: 1195–1205.PubMedCrossRefGoogle Scholar
  318. 318.
    Atkins MB, Robertson MJ, Gordon M et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res 1997; 3: 409–417.PubMedGoogle Scholar
  319. 319.
    Portielje JE, Kruit WH, Schuler M et al. Phase I study of subcutaneously administered recombinant human interleukin 12 in patients with advanced renal cell cancer. Clin Cancer Res 1999; 5: 3983–3989.PubMedGoogle Scholar
  320. 320.
    Gollob JA, Mier JW, Veenstra K et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res 2000; 6: 1678–1692.PubMedGoogle Scholar
  321. 321.
    Gollob JA, Veenstra KG, Parker RA et al. Phase I trial of concurrent twice-weekly recombinant human interleukin-12 plus low-dose IL-2 in patients with melanoma or renal cell carcinoma. J Clin Oncol 2003; 21: 2564–2573.PubMedCrossRefGoogle Scholar
  322. 322.
    Alatrash G, Hutson TE, Molto L et al. Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J Clin Oncol 2004; 22: 2891–2900.PubMedCrossRefGoogle Scholar
  323. 323.
    Wadler S, Levy D, Frederickson HL et al. A phase II trial of interleukin-12 in patients with advanced cervical cancer: clinical and immunologic correlates. Eastern Cooperative Oncology Group study E1E96. Gynecol Oncol 2004; 92: 957–964.PubMedCrossRefGoogle Scholar
  324. 324.
    Younes A, Pro B, Robertson MJ et al. Phase II clinical trial of interleukin-12 in patients with relapsed and refractory non-Hodgkin’s lymphoma and Hodgkin’s disease. Clin Cancer Res 2004; 10: 5432–5438.PubMedCrossRefGoogle Scholar
  325. 325.
    Lee KH, Wang E, Nielsen MB et al. Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J Immunol 1999; 163: 6292–6300.PubMedGoogle Scholar
  326. 326.
    Lee P, Wang F, Kuniyoshi J et al. Effects of interleukin-12 on the immune response to a multipeptide vaccine for resected metastatic melanoma. J Clin Oncol 2001; 19: 3836–3847.PubMedGoogle Scholar
  327. 327.
    Boyer JD, Cohen AD, Ugen KE et al. Therapeutic immunization of HIV-infected chimpanzees using HIV-1 plasmid antigens and interleukin-12 expressing plasmids. Aids 2000; 14: 1515–1522.PubMedCrossRefGoogle Scholar
  328. 328.
    Grabstein KH, Eisenman J, Shanebeck K et al. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 1994; 264: 965–968.PubMedCrossRefGoogle Scholar
  329. 329.
    Burton JD, Bamford RN, Peters C et al. A lymphokine, provisionally designated interleukin T and produced by a human adult T-cell leukemia line, stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci U S A 1994; 91: 4935–4939.PubMedCrossRefGoogle Scholar
  330. 330.
    Bamford RN, Grant AJ, Burton JD et al. The interleukin (IL) 2 receptor beta chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci U S A 1994; 91: 4940–4944.PubMedCrossRefGoogle Scholar
  331. 331.
    Waldmann T, Tagaya Y, Bamford R. Interleukin-2, interleukin-15, and their receptors. Int Rev Immunol 1998; 16: 205–226.PubMedGoogle Scholar
  332. 332.
    Bazan JF. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci U S A 1990; 87: 6934–6938.PubMedCrossRefGoogle Scholar
  333. 333.
    Bazan JF. Haemopoietic receptors and helical cytokines. Immunol Today 1990; 11: 350–354.PubMedCrossRefGoogle Scholar
  334. 334.
    Carson WE, Giri JG, Lindemann MJ et al. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med 1994; 180: 1395–1403.PubMedCrossRefGoogle Scholar
  335. 335.
    Anderson DM, Kumaki S, Ahdieh M et al. Functional characterization of the human interleukin-15 receptor alpha chain and close linkage of IL15RA and IL2RA genes. J Biol Chem 1995; 270: 29862–29869.PubMedCrossRefGoogle Scholar
  336. 336.
    Kim JJ, Trivedi NN, Nottingham LK et al. Modulation of amplitude and direction of in vivo immune responses by co-administration of cytokine gene expression cassettes with DNA immunogens. Eur J Immunol 1998; 28: 1089–1103.PubMedCrossRefGoogle Scholar
  337. 337.
    Xin KQ, Hamajima K, Sasaki S et al. IL-15 expression plasmid enhances cell-mediated immunity induced by an HIV-1 DNA vaccine. Vaccine 1999; 17: 858–866.PubMedCrossRefGoogle Scholar
  338. 338.
    Moore AC, Kong WP, Chakrabarti BK, Nabel GJ. Effects of antigen and genetic adjuvants on immune responses to human immunodeficiency virus DNA vaccines in mice. J Virol 2002; 76: 243–250.PubMedCrossRefGoogle Scholar
  339. 339.
    McKee HJ, T’Sao P Y, Vera M et al. Durable cytotoxic immune responses against gp120 elicited by recombinant SV40 vectors encoding HIV-1 gp120 +/- IL-15. Genet Vaccines Ther 2004; 2: 10.PubMedCrossRefGoogle Scholar
  340. 340.
    Oh S, Berzofsky JA, Burke DS et al. Coadministration of HIV vaccine vectors with vaccinia viruses expressing IL-15 but not IL-2 induces long-lasting cellular immunity. Proc Natl Acad Sci U S A 2003; 100: 3392–3397.PubMedCrossRefGoogle Scholar
  341. 341.
    Villinger F, Miller R, Mori K et al. IL-15 is superior to IL-2 in the generation of long-lived antigen specific memory CD4 and CD8 T cells in rhesus macaques. Vaccine 2004; 22: 3510–3521.PubMedCrossRefGoogle Scholar
  342. 342.
    Cui FD, Asada H, Jin ML et al. Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice. Gene Ther 2004.Google Scholar
  343. 343.
    Kwissa M, Kroger A, Hauser H et al. Cytokine-facilitated priming of CD8+ T cell responses by DNA vaccination. J Mol Med 2003; 81: 91–101.PubMedCrossRefGoogle Scholar
  344. 344.
    Dinarello CA. Interleukin-18. Methods 1999; 19: 121–132.PubMedCrossRefGoogle Scholar
  345. 345.
    Akira S. The role of IL-18 in innate immunity. Curr Opin Immunol 2000; 12: 59–63.PubMedCrossRefGoogle Scholar
  346. 346.
    McInnes IB, Gracie JA, Leung BP et al. Interleukin 18: a pleiotropic participant in chronic inflammation. Immunol Today 2000; 21: 312–315.PubMedCrossRefGoogle Scholar
  347. 347.
    Bazan JF, Timans JC, Kastelein RA. A newly defined interleukin-1? Nature 1996; 379: 591.PubMedCrossRefGoogle Scholar
  348. 348.
    Gu Y, Kuida K, Tsutsui H et al. Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Science 1997; 275: 206–209.PubMedCrossRefGoogle Scholar
  349. 349.
    Ghayur T, Banerjee S, Hugunin M et al. Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 1997; 386: 619–623.PubMedCrossRefGoogle Scholar
  350. 350.
    Puren AJ, Razeghi P, Fantuzzi G, Dinarello CA. Interleukin-18 enhances lipopolysaccharide-induced interferon-gamma production in human whole blood cultures. J Infect Dis 1998; 178: 1830–1834.PubMedCrossRefGoogle Scholar
  351. 351.
    Takeda K, Tsutsui H, Yoshimoto T et al. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 1998; 8: 383–390.PubMedCrossRefGoogle Scholar
  352. 352.
    Hyodo Y, Matsui K, Hayashi N et al. IL-18 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J Immunol 1999; 162: 1662–1668.PubMedGoogle Scholar
  353. 353.
    Fantuzzi G, Puren AJ, Harding MW et al. Interleukin-18 regulation of interferon gamma production and cell proliferation as shown in interleukin-1beta-converting enzyme (caspase-1)-deficient mice. Blood 1998; 91: 2118–2125.PubMedGoogle Scholar
  354. 354.
    Okamura H, Tsutsi H, Komatsu T et al. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995; 378: 88–91.PubMedCrossRefGoogle Scholar
  355. 355.
    Ushio S, Namba M, Okura T et al. Cloning of the cDNA for human IFN-gamma-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol 1996; 156: 4274–4279.PubMedGoogle Scholar
  356. 356.
    Robinson D, Shibuya K, Mui A et al. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NFkappaB. Immunity 1997; 7: 571–581.PubMedCrossRefGoogle Scholar
  357. 357.
    Yoshimoto T, Takeda K, Tanaka T et al. IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 1998; 161: 3400–3407.PubMedGoogle Scholar
  358. 358.
    Ahn HJ, Maruo S, Tomura M et al. A mechanism underlying synergy between IL-12 and IFN-gamma-inducing factor in enhanced production of IFN-gamma. J Immunol 1997; 159: 2125–2131.PubMedGoogle Scholar
  359. 359.
    Barbulescu K, Becker C, Schlaak JF et al. IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-gamma promoter in primary CD4+ T lymphocytes. J Immunol 1998; 160: 3642–3647.PubMedGoogle Scholar
  360. 360.
    Bohn E, Sing A, Zumbihl R et al. IL-18 (IFN-gamma-inducing factor) regulates early cytokine production in, and promotes resolution of, bacterial infection in mice. J Immunol 1998; 160: 299–307.PubMedGoogle Scholar
  361. 361.
    Lauw FN, Dekkers PE, te Velde AA et al. Interleukin-12 induces sustained activation of multiple host inflammatory mediator systems in chimpanzees. J Infect Dis 1999; 179: 646–652.PubMedCrossRefGoogle Scholar
  362. 362.
    Nagai H, Hara I, Horikawa T et al. Antitumor effects on mouse melanoma elicited by local secretion of interleukin-12 and their enhancement by treatment with interleukin-18. Cancer Invest 2000; 18: 206–213.PubMedGoogle Scholar
  363. 363.
    Yamanaka R, Tsuchiya N, Yajima N et al. Induction of an antitumor immunological response by an intratumoral injection of dendritic cells pulsed with genetically engineered Semliki Forest virus to produce interleukin-18 combined with the systemic administration of interleukin-12. J Neurosurg 2003; 99: 746–753.PubMedGoogle Scholar
  364. 364.
    Kishida T, Asada H, Satoh E et al. In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice. Gene Ther 2001; 8: 1234–1240.PubMedCrossRefGoogle Scholar
  365. 365.
    Asada H, Kishida T, Hirai H et al. Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex. Mol Ther 2002; 5: 609–616.PubMedCrossRefGoogle Scholar
  366. 366.
    Hikosaka S, Hara I, Miyake H et al. Antitumor effect of simultaneous transfer of interleukin-12 and interleukin-18 genes and its mechanism in a mouse bladder cancer model. Int J Urol 2004; 11: 647–652.PubMedCrossRefGoogle Scholar
  367. 367.
    Li Q, Carr AL, Donald EJ et al. Synergistic effects of IL-12 and IL-18 in skewing tumor-reactive T-cell responses towards a type 1 pattern. Cancer Res 2005; 65: 1063–1070.PubMedGoogle Scholar
  368. 368.
    Yamanaka R, Xanthopoulos KG. Induction of antigen-specific immune responses against malignant brain tumors by intramuscular injection of sindbis DNA encoding gp100 and IL-18. DNA Cell Biol 2005; 24: 317–324.PubMedCrossRefGoogle Scholar
  369. 369.
    Luo Y, Zhou H, Mizutani M et al. A DNA vaccine targeting Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against tumor recurrence. Cancer Res 2005; 65: 3419–3427.PubMedCrossRefGoogle Scholar
  370. 370.
    Ju DW, Yang Y, Tao Q et al. Interleukin-18 gene transfer increases antitumor effects of suicide gene therapy through efficient induction of antitumor immunity. Gene Ther 2000; 7: 1672–1679.PubMedCrossRefGoogle Scholar
  371. 371.
    Wang Q, Yu H, Ju DW et al. Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma. Gene Ther 2001; 8: 542–550.PubMedCrossRefGoogle Scholar
  372. 372.
    Kirkbride KC, Blobe GC. Inhibiting the TGF-beta signalling pathway as a means of cancer immunotherapy. Expert Opin Biol Ther 2003; 3: 251–261.PubMedGoogle Scholar
  373. 373.
    Iyer S, Wang ZG, Akhtari M et al. Targeting TGFbeta Signaling for Cancer Therapy. Cancer Biol Ther 2005; 4.Google Scholar
  374. 374.
    Elliott RL, Blobe GC. Role of transforming growth factor Beta in human cancer. J Clin Oncol 2005; 23: 2078–2093.PubMedCrossRefGoogle Scholar
  375. 375.
    Kehrl JH, Wakefield LM, Roberts AB et al. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med 1986; 163: 1037–1050.PubMedCrossRefGoogle Scholar
  376. 376.
    Inge TH, McCoy KM, Susskind BM et al. Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. J Immunol 1992; 148: 3847–3856.PubMedGoogle Scholar
  377. 377.
    Ebert EC. Inhibitory effects of transforming growth factor-beta (TGF-beta) on certain functions of intraepithelial lymphocytes. Clin Exp Immunol 1999; 115: 415–420.PubMedCrossRefGoogle Scholar
  378. 378.
    Ahuja SS, Paliogianni F, Yamada H et al. Effect of transforming growth factor-beta on early and late activation events in human T cells. J Immunol 1993; 150: 3109–3118.PubMedGoogle Scholar
  379. 379.
    Pardoux C, Asselin-Paturel C, Chehimi J et al. Functional interaction between TGF-beta and IL-12 in human primary allogeneic cytotoxicity and proliferative response. J Immunol 1997; 158: 136–143.PubMedGoogle Scholar
  380. 380.
    Ludviksson BR, Seegers D, Resnick AS, Strober W. The effect of TGF-beta1 on immune responses of naive versus memory CD4+ Th1/Th2 T cells. Eur J Immunol 2000; 30: 2101–2111.PubMedCrossRefGoogle Scholar
  381. 381.
    Lin JT, Martin SL, Xia L, Gorham JD. TGF-beta 1 uses distinct mechanisms to inhibit IFN-gamma expression in CD4+ T cells at priming and at recall: differential involvement of Stat4 and T-bet. J Immunol 2005; 174: 5950–5958.PubMedGoogle Scholar
  382. 382.
    Laouar Y, Sutterwala FS, Gorelik L, Flavell RA. Transforming growth factor-beta controls T helper type 1 cell development through regulation of natural killer cell interferon-gamma. Nat Immunol 2005; 6: 600–607.PubMedCrossRefGoogle Scholar
  383. 383.
    Mule JJ, Schwarz SL, Roberts AB et al. Transforming growth factor-beta inhibits the in vitro generation of lymphokine-activated killer cells and cytotoxic T cells. Cancer Immunol Immunother 1988; 26: 95–100.PubMedGoogle Scholar
  384. 384.
    Smyth MJ, Strobl SL, Young HA et al. Regulation of lymphokine-activated killer activity and pore-forming protein gene expression in human peripheral blood CD8+ T lymphocytes. Inhibition by transforming growth factor-beta. J Immunol 1991; 146: 3289–3297.PubMedGoogle Scholar
  385. 385.
    Espevik T, Figari IS, Ranges GE, Palladino MA, Jr. Transforming growth factor-beta 1 (TGF-beta 1) and recombinant human tumor necrosis factor-alpha reciprocally regulate the generation of lymphokine-activated killer cell activity. Comparison between natural porcine platelet-derived TGF-beta 1 and TGF-beta 2, and recombinant human TGF-beta 1. J Immunol 1988; 140: 2312–2316.PubMedGoogle Scholar
  386. 386.
    Espevik T, Waage A, Faxvaag A, Shalaby MR. Regulation of interleukin-2 and interleukin-6 production from T-cells: involvement of interleukin-1 beta and transforming growth factor-beta. Cell Immunol 1990; 126: 47–56.PubMedCrossRefGoogle Scholar
  387. 387.
    Fargeas C, Wu CY, Nakajima T et al. Differential effect of transforming growth factor beta on the synthesis of Th1- and Th2-like lymphokines by human T lymphocytes. Eur J Immunol 1992; 22: 2173–2176.PubMedCrossRefGoogle Scholar
  388. 388.
    Ahmadzadeh M, Rosenberg SA. TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells. J Immunol 2005; 174: 5215–5223.PubMedGoogle Scholar
  389. 389.
    Nakamura K, Kitani A, Fuss I et al. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 2004; 172: 834–842.PubMedGoogle Scholar
  390. 390.
    Su HC, Leite-Morris KA, Braun L, Biron CA. A role for transforming growth factor-beta 1 in regulating natural killer cell and T lymphocyte proliferative responses during acute infection with lymphocytic choriomeningitis virus. J Immunol 1991; 147: 2717–2727.PubMedGoogle Scholar
  391. 391.
    Lee JC, Lee KM, Kim DW, Heo DS. Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol 2004; 172: 7335–7340.PubMedGoogle Scholar
  392. 392.
    Malygin AM, Meri S, Timonen T. Regulation of natural killer cell activity by transforming growth factor-beta and prostaglandin E2. Scand J Immunol 1993; 37: 71–76.PubMedCrossRefGoogle Scholar
  393. 393.
    Bellone G, Aste-Amezaga M, Trinchieri G, Rodeck U. Regulation of NK cell functions by TGF-beta 1. J Immunol 1995; 155: 1066–1073.PubMedGoogle Scholar
  394. 394.
    Rook AH, Kehrl JH, Wakefield LM et al. Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol 1986; 136: 3916–3920.PubMedGoogle Scholar
  395. 395.
    Kuppner MC, Hamou MF, Bodmer S et al. The glioblastoma-derived T-cell suppressor factor/transforming growth factor beta 2 inhibits the generation of lymphokine-activated killer (LAK) cells. Int J Cancer 1988; 42: 562–567.PubMedCrossRefGoogle Scholar
  396. 396.
    Brooks B, Chapman K, Lawry J et al. Suppression of lymphokine-activated killer (LAK) cell induction mediated by interleukin-4 and transforming growth factor-beta 1: effect of addition of exogenous tumour necrosis factor-alpha and interferon-gamma, and measurement of their endogenous production. Clin Exp Immunol 1990; 82: 583–589.PubMedCrossRefGoogle Scholar
  397. 397.
    Strassmann G, Cole MD, Newman W. Regulation of colony-stimulating factor 1-dependent macrophage precursor proliferation by type beta transforming growth factor. J Immunol 1988; 140: 2645–2651.PubMedGoogle Scholar
  398. 398.
    Sato Y, Kobori S, Sakai M et al. Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-beta activation. Atherosclerosis 1996; 125: 15–26.PubMedCrossRefGoogle Scholar
  399. 399.
    Pinson DM, LeClaire RD, Lorsbach RB et al. Regulation by transforming growth factor-beta 1 of expression and function of the receptor for IFN-gamma on mouse macrophages. J Immunol 1992; 149: 2028–2034.PubMedGoogle Scholar
  400. 400.
    Jun CD, Choi BM, Kim SU et al. Down-regulation of transforming growth factor-beta gene expression by antisense oligodeoxynucleotides increases recombinant interferon-gamma-induced nitric oxide synthesis in murine peritoneal macrophages. Immunology 1995; 85: 114–119.PubMedGoogle Scholar
  401. 401.
    Imai K, Takeshita A, Hanazawa S. Transforming growth factor-beta inhibits lipopolysaccharide-stimulated expression of inflammatory cytokines in mouse macrophages through downregulation of activation protein 1 and CD14 receptor expression. Infect Immun 2000; 68: 2418–2423.PubMedCrossRefGoogle Scholar
  402. 402.
    Yamaguchi Y, Tsumura H, Miwa M, Inaba K. Contrasting effects of TGF-beta 1 and TNF-alpha on the development of dendritic cells from progenitors in mouse bone marrow. Stem Cells 1997; 15: 144–153.PubMedCrossRefGoogle Scholar
  403. 403.
    Sato K, Kawasaki H, Nagayama H et al. TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J Immunol 2000; 164: 2285–2295.PubMedGoogle Scholar
  404. 404.
    Maehara Y, Kakeji Y, Kabashima A et al. Role of transforming growth factor-beta 1 in invasion and metastasis in gastric carcinoma. J Clin Oncol 1999; 17: 607–614.PubMedGoogle Scholar
  405. 405.
    Pepper MS. Transforming growth factor-beta: vasculogenesis, angiogenesis, and vessel wall integrity. Cytokine Growth Factor Rev 1997; 8: 21–43.PubMedCrossRefGoogle Scholar
  406. 406.
    Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res 1997; 71: 165–207.PubMedGoogle Scholar
  407. 407.
    Becker C, Fantini MC, Schramm C et al. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 2004; 21: 491–501.PubMedCrossRefGoogle Scholar
  408. 408.
    Paterson IC, Matthews JB, Huntley S et al. Decreased expression of TGF-beta cell surface receptors during progression of human oral squamous cell carcinoma. J Pathol 2001; 193: 458–467.PubMedCrossRefGoogle Scholar
  409. 409.
    West J, Munoz-Antonia T, Johnson JG et al. Transforming growth factor-beta type II receptors and smad proteins in follicular thyroid tumors. Laryngoscope 2000; 110: 1323–1327.PubMedCrossRefGoogle Scholar
  410. 410.
    Fujiwara K, Ikeda H, Yoshimoto T. Abnormalities in expression of genes, mRNA, and proteins of transforming growth factor-beta receptor type I and type II in human pituitary adenomas. Clin Neuropathol 1998; 17: 19–26.PubMedGoogle Scholar
  411. 411.
    Park K, Kim SJ, Bang YJ et al. Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta. Proc Natl Acad Sci U S A 1994; 91: 8772–8776.PubMedCrossRefGoogle Scholar
  412. 412.
    Markowitz S, Wang J, Myeroff L et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995; 268: 1336–1338.PubMedCrossRefGoogle Scholar
  413. 413.
    Garrigue-Antar L, Munoz-Antonia T, Antonia SJ et al. Missense mutations of the transforming growth factor beta type II receptor in human head and neck squamous carcinoma cells. Cancer Res 1995; 55: 3982–3987.PubMedGoogle Scholar
  414. 414.
    Lucke CD, Philpott A, Metcalfe JC et al. Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer. Cancer Res 2001; 61: 482–485.PubMedGoogle Scholar
  415. 415.
    Kim SJ, Im YH, Markowitz SD, Bang YJ. Molecular mechanisms of inactivation of TGF-beta receptors during carcinogenesis. Cytokine Growth Factor Rev 2000; 11: 159–168.PubMedCrossRefGoogle Scholar
  416. 416.
    Imai Y, Kurokawa M, Izutsu K et al. Mutations of the Smad4 gene in acute myelogeneous leukemia and their functional implications in leukemogenesis. Oncogene 2001; 20: 88–96.PubMedCrossRefGoogle Scholar
  417. 417.
    Hu W, Wu W, Nash MA et al. Anomalies of the TGF-beta postreceptor signaling pathway in ovarian cancer cell lines. Anticancer Res 2000; 20: 729–733.PubMedGoogle Scholar
  418. 418.
    Villanueva A, Garcia C, Paules AB et al. Disruption of the antiproliferative TGF-beta signaling pathways in human pancreatic cancer cells. Oncogene 1998; 17: 1969–1978.PubMedCrossRefGoogle Scholar
  419. 419.
    Giannelli G, Fransvea E, Marinosci F et al. Transforming growth factor-beta1 triggers hepatocellular carcinoma invasiveness via alpha3beta1 integrin. Am J Pathol 2002; 161: 183–193.PubMedGoogle Scholar
  420. 420.
    Saito H, Tsujitani S, Oka S et al. An elevated serum level of transforming growth factor-beta 1 (TGF-beta 1) significantly correlated with lymph node metastasis and poor prognosis in patients with gastric carcinoma. Anticancer Res 2000; 20: 4489–4493.PubMedGoogle Scholar
  421. 421.
    Shim KS, Kim KH, Han WS, Park EB. Elevated serum levels of transforming growth factor-beta1 in patients with colorectal carcinoma: its association with tumor progression and its significant decrease after curative surgical resection. Cancer 1999; 85: 554–561.PubMedCrossRefGoogle Scholar
  422. 422.
    Guzinska-Ustymowicz K, Kemona A. Transforming growth factor beta can be a parameter of aggressiveness of pT1 colorectal cancer. World J Gastroenterol 2005; 11: 1193–1195.PubMedGoogle Scholar
  423. 423.
    Feltl D, Zavadova E, Pala M, Hozak P. The dynamics of plasma transforming growth factor beta 1 (TGF-beta1) level during radiotherapy with or without simultaneous chemotherapy in advanced head and neck cancer. Oral Oncol 2005; 41: 208–213.PubMedCrossRefGoogle Scholar
  424. 424.
    Wojtowicz-Praga S, Verma UN, Wakefield L et al. Modulation of B16 melanoma growth and metastasis by anti-transforming growth factor beta antibody and interleukin-2. J Immunother Emphasis Tumor Immunol 1996; 19: 169–175.PubMedGoogle Scholar
  425. 425.
    Gridley DS, Sura SS, Uhm JR et al. Effects of anti-transforming growth factor-beta antibody and interleukin-2 in tumor-bearing mice. Cancer Biother 1993; 8: 159–170.PubMedGoogle Scholar
  426. 426.
    Arteaga CL, Hurd SD, Winnier AR et al. Anti-transforming growth factor (TGF)-beta antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer cell activity. Implications for a possible role of tumor cell/host TGF-beta interactions in human breast cancer progression. J Clin Invest 1993; 92: 2569–2576.PubMedGoogle Scholar
  427. 427.
    Ohmori T, Yang JL, Price JO, Arteaga CL. Blockade of tumor cell transforming growth factor-betas enhances cell cycle progression and sensitizes human breast carcinoma cells to cytotoxic chemotherapy. Exp Cell Res 1998; 245: 350–359.PubMedCrossRefGoogle Scholar
  428. 428.
    Mao XW, Kettering JD, Gridley DS. Immunotherapy with low-dose interleukin-2 and anti-transforming growth factor-beta antibody in a murine tumor model. Cancer Biother 1994; 9: 317–327.PubMedGoogle Scholar
  429. 429.
    Jia ZC, Zou LY, Ni B et al. Effective induction of antitumor immunity by immunization with plasmid DNA encoding TRP-2 plus neutralization of TGF-beta. Cancer Immunol Immunother 2005; 54: 446–452.PubMedCrossRefGoogle Scholar
  430. 430.
    Suzuki E, Kapoor V, Cheung HK et al. Soluble type II transforming growth factor-beta receptor inhibits established murine malignant mesothelioma tumor growth by augmenting host antitumor immunity. Clin Cancer Res 2004; 10: 5907–5918.PubMedCrossRefGoogle Scholar
  431. 431.
    Rowland-Goldsmith MA, Maruyama H, Kusama T et al. Soluble type II transforming growth factor-beta (TGF-beta) receptor inhibits TGF-beta signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. Clin Cancer Res 2001; 7: 2931–2940.PubMedGoogle Scholar
  432. 432.
    Rowland-Goldsmith MA, Maruyama H, Matsuda K et al. Soluble type II transforming growth factor-beta receptor attenuates expression of metastasis-associated genes and suppresses pancreatic cancer cell metastasis. Mol Cancer Ther 2002; 1: 161–167.PubMedGoogle Scholar
  433. 433.
    Yang YA, Dukhanina O, Tang B et al. Lifetime exposure to a soluble TGF-beta antagonist protects mice against metastasis without adverse side effects. J Clin Invest 2002; 109: 1607–1615.PubMedCrossRefGoogle Scholar
  434. 434.
    Bandyopadhyay A, Zhu Y, Cibull ML et al. A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells. Cancer Res 1999; 59: 5041–5046.PubMedGoogle Scholar
  435. 435.
    Won J, Kim H, Park EJ et al. Tumorigenicity of mouse thymoma is suppressed by soluble type II transforming growth factor beta receptor therapy. Cancer Res 1999; 59: 1273–1277.PubMedGoogle Scholar
  436. 436.
    Tuxhorn JA, McAlhany SJ, Yang F et al. Inhibition of transforming growth factor-beta activity decreases angiogenesis in a human prostate cancer-reactive stroma xenograft model. Cancer Res 2002; 62: 6021–6025.PubMedGoogle Scholar
  437. 437.
    Biglari A, Bataille D, Naumann U et al. Effects of ectopic decorin in modulating intracranial glioma progression in vivo, in a rat syngeneic model. Cancer Gene Ther 2004; 11: 721–732.PubMedCrossRefGoogle Scholar
  438. 438.
    Engel S, Isenmann S, Stander M et al. Inhibition of experimental rat glioma growth by decorin gene transfer is associated with decreased microglial infiltration. J Neuroimmunol 1999; 99: 13–18.PubMedCrossRefGoogle Scholar
  439. 439.
    Stander M, Naumann U, Dumitrescu L et al. Decorin gene transfer-mediated suppression of TGF-beta synthesis abrogates experimental malignant glioma growth in vivo. Gene Ther 1998; 5: 1187–1194.PubMedCrossRefGoogle Scholar
  440. 440.
    Yamaguchi Y, Mann DM, Ruoslahti E. Negative regulation of transforming growth factor-beta by the proteoglycan decorin. Nature 1990; 346: 281–284.PubMedCrossRefGoogle Scholar
  441. 441.
    Park JA, Wang E, Kurt RA et al. Expression of an antisense transforming growth factor-beta1 transgene reduces tumorigenicity of EMT6 mammary tumor cells. Cancer Gene Ther 1997; 4: 42–50.PubMedGoogle Scholar
  442. 442.
    Liau LM, Fakhrai H, Black KL. Prolonged survival of rats with intracranial C6 gliomas by treatment with TGF-beta antisense gene. Neurol Res 1998; 20: 742–747.PubMedGoogle Scholar
  443. 443.
    Dorigo O, Shawler DL, Royston I et al. Combination of transforming growth factor beta antisense and interleukin-2 gene therapy in the murine ovarian teratoma model. Gynecol Oncol 1998; 71: 204–210.PubMedCrossRefGoogle Scholar
  444. 444.
    Maggard M, Meng L, Ke B et al. Antisense TGF-beta2 immunotherapy for hepatocellular carcinoma: treatment in a rat tumor model. Ann Surg Oncol 2001; 8: 32–37.PubMedGoogle Scholar
  445. 445.
    Marzo AL, Fitzpatrick DR, Robinson BW, Scott B. Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo. Cancer Res 1997; 57: 3200–3207.PubMedGoogle Scholar
  446. 446.
    Schlingensiepen R, Goldbrunner M, Szyrach MN et al. Intracerebral and Intrathecal Infusion of the TGF-beta2-Specific Antisense Phosphorothioate Oligonucleotide AP 12009 in Rabbits and Primates: Toxicology and Safety. Oligonucleotides 2005; 15: 94–104.PubMedCrossRefGoogle Scholar
  447. 447.
    Shah AH, Tabayoyong WB, Kundu SD et al. Suppression of tumor metastasis by blockade of transforming growth factor beta signaling in bone marrow cells through a retroviral-mediated gene therapy in mice. Cancer Res 2002; 62: 7135–7138.PubMedGoogle Scholar
  448. 448.
    Zhang Q, Yang X, Pins M et al. Adoptive transfer of tumor-reactive transforming growth factor-beta-insensitive CD8+ T cells: eradication of autologous mouse prostate cancer. Cancer Res 2005; 65: 1761–1769.PubMedCrossRefGoogle Scholar
  449. 449.
    Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med 2001; 7: 1118–1122.PubMedCrossRefGoogle Scholar
  450. 450.
    Siriwardena D, Khaw PT, King AJ et al. Human antitransforming growth factor beta(2) monoclonal antibody–a new modulator of wound healing in trabeculectomy: a randomized placebo controlled clinical study. Ophthalmology 2002; 109: 427–431.PubMedCrossRefGoogle Scholar
  451. 451.
    Schlingensiepen KH, Schlingensiepen R, Steinbrecher A et al. Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009. Cytokine Growth Factor Rev 2005.Google Scholar
  452. 452.
    Sabat R, Asadullah K. Interleukin-10 in Cancer Immunity. In Stuhler G, Walden P (eds): Cancer immune therapy: current and future strategies, Edition Weinheim: Wiley-VCH 2002; 155–175.Google Scholar
  453. 453.
    Becker JC, Czerny C, Brocker EB. Maintenance of clonal anergy by endogenously produced IL-10. Int Immunol 1994; 6: 1605–1612.PubMedCrossRefGoogle Scholar
  454. 454.
    Cooper MA, Fehniger TA, Turner SC et al. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 2001; 97: 3146–3151.PubMedCrossRefGoogle Scholar
  455. 455.
    Buchwald UK, Geerdes-Fenge HF, Vockler J et al. Interleukin-10: effects on phagocytosis and adhesion molecule expression of granulocytes and monocytes in a comparison with prednisolone. Eur J Med Res 1999; 4: 85–94.PubMedGoogle Scholar
  456. 456.
    Carson WE, Lindemann MJ, Baiocchi R et al. The functional characterization of interleukin-10 receptor expression on human natural killer cells. Blood 1995; 85: 3577–3585.PubMedGoogle Scholar
  457. 457.
    Hart PH, Hunt EK, Bonder CS et al. Regulation of surface and soluble TNF receptor expression on human monocytes and synovial fluid macrophages by IL-4 and IL-10. J Immunol 1996; 157: 3672–3680.PubMedGoogle Scholar
  458. 458.
    de Waal Malefyt R, Yssel H, de Vries JE. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol 1993; 150: 4754–4765.Google Scholar
  459. 459.
    Creery WD, Diaz-Mitoma F, Filion L, Kumar A. Differential modulation of B7–1 and B7–2 isoform expression on human monocytes by cytokines which influence the development of T helper cell phenotype. Eur J Immunol 1996; 26: 1273–1277.PubMedCrossRefGoogle Scholar
  460. 460.
    Willems F, Marchant A, Delville JP et al. Interleukin-10 inhibits B7 and intercellular adhesion molecule-1 expression on human monocytes. Eur J Immunol 1994; 24: 1007–1009.PubMedCrossRefGoogle Scholar
  461. 461.
    Buelens C, Verhasselt V, De Groote D et al. Interleukin-10 prevents the generation of dendritic cells from human peripheral blood mononuclear cells cultured with interleukin-4 and granulocyte/macrophage-colony-stimulating factor. Eur J Immunol 1997; 27: 756–762.PubMedCrossRefGoogle Scholar
  462. 462.
    Allavena P, Piemonti L, Longoni D et al. IL-10 prevents the differentiation of monocytes to dendritic cells but promotes their maturation to macrophages. Eur J Immunol 1998; 28: 359–369.PubMedCrossRefGoogle Scholar
  463. 463.
    Corinti S, Albanesi C, la Sala A et al. Regulatory activity of autocrine IL-10 on dendritic cell functions. J Immunol 2001; 166: 4312–4318.PubMedGoogle Scholar
  464. 464.
    Gerlini G, Tun-Kyi A, Dudli C et al. Metastatic melanoma secreted IL-10 down-regulates CD1 molecules on dendritic cells in metastatic tumor lesions. Am J Pathol 2004; 165: 1853–1863.PubMedGoogle Scholar
  465. 465.
    Taga K, Mostowski H, Tosato G. Human interleukin-10 can directly inhibit T-cell growth. Blood 1993; 81: 2964–2971.PubMedGoogle Scholar
  466. 466.
    Klein B, Lu ZY, Gu ZJ et al. Interleukin-10 and Gp130 cytokines in human multiple myeloma. Leuk Lymphoma 1999; 34: 63–70.PubMedGoogle Scholar
  467. 467.
    Beatty PR, Krams SM, Martinez OM. Involvement of IL-10 in the autonomous growth of EBV-transformed B cell lines. J Immunol 1997; 158: 4045–4051.PubMedGoogle Scholar
  468. 468.
    Czarneski J, Lin YC, Chong S et al. Studies in NZB IL-10 knockout mice of the requirement of IL-10 for progression of B-cell lymphoma. Leukemia 2004; 18: 597–606.PubMedCrossRefGoogle Scholar
  469. 469.
    Huang M, Stolina M, Sharma S et al. Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: up-regulation of interleukin 10 and down-regulation of interleukin 12 production. Cancer Res 1998; 58: 1208–1216.PubMedGoogle Scholar
  470. 470.
    Smith DR, Kunkel SL, Burdick MD et al. Production of interleukin-10 by human bronchogenic carcinoma. Am J Pathol 1994; 145: 18–25.PubMedGoogle Scholar
  471. 471.
    Sato T, McCue P, Masuoka K et al. Interleukin 10 production by human melanoma. Clin Cancer Res 1996; 2: 1383–1390.PubMedGoogle Scholar
  472. 472.
    Huettner C, Czub S, Kerkau S et al. Interleukin 10 is expressed in human gliomas in vivo and increases glioma cell proliferation and motility in vitro. Anticancer Res 1997; 17: 3217–3224.PubMedGoogle Scholar
  473. 473.
    Mori N, Prager D. Interleukin-10 gene expression and adult T-cell leukemia. Leuk Lymphoma 1998; 29: 239–248.PubMedCrossRefGoogle Scholar
  474. 474.
    Bargou RC, Mapara MY, Zugck C et al. Characterization of a novel Hodgkin cell line, HD-MyZ, with myelomonocytic features mimicking Hodgkin’s disease in severe combined immunodeficient mice. J Exp Med 1993; 177: 1257–1268.PubMedCrossRefGoogle Scholar
  475. 475.
    Voorzanger N, Touitou R, Garcia E et al. Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin’s lymphoma cells and act as cooperative growth factors. Cancer Res 1996; 56: 5499–5505.PubMedGoogle Scholar
  476. 476.
    Ortegel JW, Staren ED, Faber LP et al. Cytokine biosynthesis by tumor-infiltrating T lymphocytes from human non-small-cell lung carcinoma. Cancer Immunol Immunother 2000; 48: 627–634.PubMedCrossRefGoogle Scholar
  477. 477.
    Blay JY, Burdin N, Rousset F et al. Serum interleukin-10 in non-Hodgkin’s lymphoma: a prognostic factor. Blood 1993; 82: 2169–2174.PubMedGoogle Scholar
  478. 478.
    Fayad L, Keating MJ, Reuben JM et al. Interleukin-6 and interleukin-10 levels in chronic lymphocytic leukemia: correlation with phenotypic characteristics and outcome. Blood 2001; 97: 256–263.PubMedCrossRefGoogle Scholar
  479. 479.
    Bohlen H, Kessler M, Sextro M et al. Poor clinical outcome of patients with Hodgkin’s disease and elevated interleukin-10 serum levels. Clinical significance of interleukin-10 serum levels for Hodgkin’s disease. Ann Hematol 2000; 79: 110–113.PubMedCrossRefGoogle Scholar
  480. 480.
    Visco C, Vassilakopoulos TP, Kliche KO et al. Elevated serum levels of IL-10 are associated with inferior progression-free survival in patients with Hodgkin’s disease treated with radiotherapy. Leuk Lymphoma 2004; 45: 2085–2092.PubMedCrossRefGoogle Scholar
  481. 481.
    Asadullah K, Docke WD, Haeussler A et al. Progression of mycosis fungoides is associated with increasing cutaneous expression of interleukin-10 mRNA. J Invest Dermatol 1996; 107: 833–837.PubMedCrossRefGoogle Scholar
  482. 482.
    Neuner A, Schindel M, Wildenberg U et al. Prognostic significance of cytokine modulation in non-small cell lung cancer. Int J Cancer 2002; 101: 287–292.PubMedCrossRefGoogle Scholar
  483. 483.
    Galizia G, Lieto E, De Vita F et al. Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. J Interferon Cytokine Res 2002; 22: 473–482.PubMedCrossRefGoogle Scholar
  484. 484.
    Nemunaitis J, Fong T, Shabe P et al. Comparison of serum interleukin-10 (IL-10) levels between normal volunteers and patients with advanced melanoma. Cancer Invest 2001; 19: 239–247.PubMedCrossRefGoogle Scholar
  485. 485.
    Chau GY, Wu CW, Lui WY et al. Serum interleukin-10 but not interleukin-6 is related to clinical outcome in patients with resectable hepatocellular carcinoma. Ann Surg 2000; 231: 552–558.PubMedCrossRefGoogle Scholar
  486. 486.
    De Vita F, Orditura M, Galizia G et al. Serum interleukin-10 is an independent prognostic factor in advanced solid tumors. Oncol Rep 2000; 7: 357–361.PubMedGoogle Scholar
  487. 487.
    Cunningham LM, Chapman C, Dunstan R et al. Polymorphisms in the interleukin 10 gene promoter are associated with susceptibility to aggressive non-Hodgkin’s lymphoma. Leuk Lymphoma 2003; 44: 251–255.PubMedCrossRefGoogle Scholar
  488. 488.
    Havranek E, Howell WM, Fussell HM et al. An interleukin-10 promoter polymorphism may influence tumor development in renal cell carcinoma. J Urol 2005; 173: 709–712.PubMedCrossRefGoogle Scholar
  489. 489.
    Langsenlehner U, Krippl P, Renner W et al. Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk. Breast Cancer Res Treat 2005; 90: 113–115.PubMedCrossRefGoogle Scholar
  490. 490.
    Stearns ME, Kim G, Garcia F, Wang M. Interleukin-10 induced activating transcription factor 3 transcriptional suppression of matrix metalloproteinase-2 gene expression in human prostate CPTX-1532 Cells. Mol Cancer Res 2004; 2: 403–416.PubMedGoogle Scholar
  491. 491.
    Zheng LM, Ojcius DM, Garaud F et al. Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. J Exp Med 1996; 184: 579–584.PubMedCrossRefGoogle Scholar
  492. 492.
    Vicari AP, Trinchieri G. Interleukin-10 in viral diseases and cancer: exiting the labyrinth? Immunol Rev 2004; 202: 223–236.PubMedCrossRefGoogle Scholar
  493. 493.
    Baj-Krzyworzeka M, Baran J, Szatanek R et al. Prevention and reversal of tumor cell-induced monocyte deactivation by cytokines, purified protein derivative (PPD), and anti-IL-10 antibody. Cancer Immun 2004; 4: 8.Google Scholar
  494. 494.
    Stassi G, Todaro M, Zerilli M et al. Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10. Cancer Res 2003; 63: 6784–6790.PubMedGoogle Scholar
  495. 495.
    Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin’s lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res 2001; 61: 5137–5144.PubMedGoogle Scholar
  496. 496.
    Alas S, Emmanouilides C, Bonavida B. Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin Cancer Res 2001; 7: 709–723.PubMedGoogle Scholar
  497. 497.
    Garcia-Hernandez ML, Hernandez-Pando R, Gariglio P, Berumen J. Interleukin-10 promotes B16-melanoma growth by inhibition of macrophage functions and induction of tumour and vascular cell proliferation. Immunology 2002; 105: 231–243.PubMedCrossRefGoogle Scholar
  498. 498.
    Hagenbaugh A, Sharma S, Dubinett SM et al. Altered immune responses in interleukin 10 transgenic mice. J Exp Med 1997; 185: 2101–2110.PubMedCrossRefGoogle Scholar
  499. 499.
    Seo N, Hayakawa S, Takigawa M, Tokura Y. Interleukin-10 expressed at early tumour sites induces subsequent generation of CD4(+) T-regulatory cells and systemic collapse of antitumour immunity. Immunology 2001; 103: 449–457.PubMedCrossRefGoogle Scholar
  500. 500.
    Specht C, Bexten S, Kolsch E, Pauels HG. Prostaglandins, but not tumor-derived IL-10, shut down concomitant tumor-specific CTL responses during murine plasmacytoma progression. Int J Cancer 2001; 91: 705–712.PubMedCrossRefGoogle Scholar
  501. 501.
    Loercher AE, Nash MA, Kavanagh JJ et al. Identification of an IL-10-producing HLA-DR-negative monocyte subset in the malignant ascites of patients with ovarian carcinoma that inhibits cytokine protein expression and proliferation of autologous T cells. J Immunol 1999; 163: 6251–6260.PubMedGoogle Scholar
  502. 502.
    Qin Z, Noffz G, Mohaupt M, Blankenstein T. Interleukin-10 prevents dendritic cell accumulation and vaccination with granulocyte-macrophage colony-stimulating factor gene-modified tumor cells. J Immunol 1997; 159: 770–776.PubMedGoogle Scholar
  503. 503.
    Kim BG, Joo HG, Chung IS et al. Inhibition of interleukin-10 (IL-10) production from MOPC 315 tumor cells by IL-10 antisense oligodeoxynucleotides enhances cell-mediated immune responses. Cancer Immunol Immunother 2000; 49: 433–440.PubMedCrossRefGoogle Scholar
  504. 504.
    Liu G, Ng H, Akasaki Y et al. Small interference RNA modulation of IL-10 in human monocyte-derived dendritic cells enhances the Th1 response. Eur J Immunol 2004; 34: 1680–1687.PubMedCrossRefGoogle Scholar
  505. 505.
    He Q, Moore TT, Eko FO et al. Molecular basis for the potency of IL-10-deficient dendritic cells as a highly efficient APC system for activating Th1 response. J Immunol 2005; 174: 4860–4869.PubMedGoogle Scholar
  506. 506.
    Llorente L, Richaud-Patin Y, Garcia-Padilla C et al. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic lupus erythematosus. Arthritis Rheum 2000; 43: 1790–1800.PubMedCrossRefGoogle Scholar
  507. 507.
    Terabe M, Park JM, Berzofsky JA. Role of IL-13 in regulation of anti-tumor immunity and tumor growth. Cancer Immunol Immunother 2004; 53: 79–85.PubMedCrossRefGoogle Scholar
  508. 508.
    Wynn TA. IL-13 effector functions. Annu Rev Immunol 2003; 21: 425–456.PubMedCrossRefGoogle Scholar
  509. 509.
    McKenzie AN, Li X, Largaespada DA et al. Structural comparison and chromosomal localization of the human and mouse IL-13 genes. J Immunol 1993; 150: 5436–5444.PubMedGoogle Scholar
  510. 510.
    Obiri NI, Debinski W, Leonard WJ, Puri RK. Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that does not involve the common gamma chain shared by receptors for interleukins 2, 4, 7, 9, and 15. J Biol Chem 1995; 270: 8797–8804.PubMedCrossRefGoogle Scholar
  511. 511.
    Aman MJ, Tayebi N, Obiri NI et al. cDNA cloning and characterization of the human interleukin 13 receptor alpha chain. J Biol Chem 1996; 271: 29265–29270.PubMedCrossRefGoogle Scholar
  512. 512.
    Hilton DJ, Zhang JG, Metcalf D et al. Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci U S A 1996; 93: 497–501.PubMedCrossRefGoogle Scholar
  513. 513.
    Chiaramonte MG, Mentink-Kane M, Jacobson BA et al. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. J Exp Med 2003; 197: 687–701.PubMedCrossRefGoogle Scholar
  514. 514.
    Wood N, Whitters MJ, Jacobson BA et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor alpha 2. J Exp Med 2003; 197: 703–709.PubMedCrossRefGoogle Scholar
  515. 515.
    Punnonen J, Aversa G, Cocks BG et al. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci U S A 1993; 90: 3730–3734.PubMedCrossRefGoogle Scholar
  516. 516.
    de Waal Malefyt R, Figdor CG, Huijbens R et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol 1993; 151: 6370–6381.Google Scholar
  517. 517.
    Smyth MJ, Crowe NY, Pellicci DG et al. Sequential production of interferon-gamma by NK1.1(+) T cells and natural killer cells is essential for the antimetastatic effect of alpha-galactosylceramide. Blood 2002; 99: 1259–1266.PubMedCrossRefGoogle Scholar
  518. 518.
    Terabe M, Matsui S, Noben-Trauth N et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol 2000; 1: 515–520.PubMedCrossRefGoogle Scholar
  519. 519.
    Terabe M, Matsui S, Park JM et al. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med 2003; 198: 1741–1752.PubMedCrossRefGoogle Scholar
  520. 520.
    Skinnider BF, Kapp U, Mak TW. The role of interleukin 13 in classical Hodgkin lymphoma. Leuk Lymphoma 2002; 43: 1203–1210.PubMedCrossRefGoogle Scholar
  521. 521.
    Kawakami K, Kawakami M, Snoy PJ et al. In vivo overexpression of IL-13 receptor alpha2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Exp Med 2001; 194: 1743–1754.PubMedCrossRefGoogle Scholar
  522. 522.
    Lebel-Binay S, Laguerre B, Quintin-Colonna F et al. Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin-13. Eur J Immunol 1995; 25: 2340–2348.PubMedCrossRefGoogle Scholar
  523. 523.
    Kacha AK, Fallarino F, Markiewicz MA, Gajewski TF. Cutting edge: spontaneous rejection of poorly immunogenic P1.HTR tumors by Stat6-deficient mice. J Immunol 2000; 165: 6024–6028.PubMedGoogle Scholar
  524. 524.
    Ostrand-Rosenberg S, Clements VK, Terabe M et al. Resistance to metastatic disease in STAT6-deficient mice requires hemopoietic and nonhemopoietic cells and is IFN-gamma dependent. J Immunol 2002; 169: 5796–5804.PubMedGoogle Scholar
  525. 525.
    Rainov NG, Soling A. Technology evaluation: cintredekin besudotox, NeoPharm/Nippon. Curr Opin Mol Ther 2005; 7: 170–181.PubMedGoogle Scholar
  526. 526.
    Hodge JW, Chakraborty M, Kudo-Saito C et al. Multiple costimulatory modalities enhance CTL avidity. J Immunol 2005; 174: 5994–6004.PubMedGoogle Scholar
  527. 527.
    Ogden CA, Pound JD, Batth BK et al. Enhanced apoptotic cell clearance capacity and B cell survival factor production by IL-10-activated macrophages: implications for Burkitt’s lymphoma. J Immunol 2005; 174: 3015–3023.PubMedGoogle Scholar
  528. 528.
    Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol 2002; 129: 263–276.PubMedCrossRefGoogle Scholar
  529. 529.
    Taga K, Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 1992; 148: 1143–1148.PubMedGoogle Scholar
  530. 530.
    Matsuda M, Salazar F, Petersson M et al. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med 1994; 180: 2371–2376.PubMedCrossRefGoogle Scholar
  531. 531.
    Mocellin S, Panelli M, Wang E et al. IL-10 stimulatory effects on human NK cells explored by gene profile analysis. Genes Immun 2004; 5: 621–630.PubMedCrossRefGoogle Scholar
  532. 532.
    Piemonti L, Bernasconi S, Luini W et al. IL-13 supports differentiation of dendritic cells from circulating precursors in concert with GM-CSF. Eur Cytokine Netw 1995; 6: 245–252.PubMedGoogle Scholar
  533. 533.
    Lutz MB, Schnare M, Menges M et al. Differential functions of IL-4 receptor types I and II for dendritic cell maturation and IL-12 production and their dependency on GM-CSF. J Immunol 2002; 169: 3574–3580.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Yvonne M. Saenger
    • 1
  • Robert R. Jenq
    • 1
  • Miguel-Angel Perales
    • 1
  1. 1.Memorial Sloan-Kettering Cancer CenterAnd Weill Medical School and Graduate School of Cornell University 1275 York AvenueNew YorkUSA

Personalised recommendations