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Checkpoint Blockade and Combinatorial Immunotherapies

  • Karl S. Peggs
  • Sergio A. Quezada
  • James P. Allison

Keywords

Antitumor Immunity Antitumor Response CTLA4 Blockade Denileukin Diftitox Cellular Vaccine 
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.

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References

  1. 1.
    Hao,Y., Legrand,N., & Freitas,A.A. (2006) The clone size of peripheral CD8 T cells is regulated by TCR promiscuity. J.Exp.Med.Google Scholar
  2. 2.
    Watanabe,N., Gavrieli,M., Sedy,J.R., Yang,J., Fallarino,F., Loftin,S.K., Hurchla,M.A., Zimmerman,N., Sim,J., Zang,X., Murphy,T.L., Russell,J.H., Allison,J.P., & Murphy,K.M. (2003) BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat.Immunol., 4, 670–679.PubMedGoogle Scholar
  3. 3.
    Marrogi,A.J., Munshi,A., Merogi,A.J., Ohadike,Y., El Habashi,A., Marrogi,O.L., & Freeman,S.M. (1997) Study of tumor infiltrating lymphocytes and transforming growth factor-beta as prognostic factors in breast carcinoma. Int.J.Cancer, 74, 492–501.PubMedGoogle Scholar
  4. 4.
    Zhang,L., Conejo-Garcia,J.R., Katsaros,D., Gimotty,P.A., Massobrio,M., Regnani,G., Makrigiannakis,A., Gray,H., Schlienger,K., Liebman,M.N., Rubin,S.C., & Coukos,G. (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N.Engl.J.Med., 348, 203–213.PubMedGoogle Scholar
  5. 5.
    Nakano,O., Sato,M., Naito,Y., Suzuki,K., Orikasa,S., Aizawa,M., Suzuki,Y., Shintaku,I., Nagura,H., & Ohtani,H. (2001) Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res., 61, 5132–5136.PubMedGoogle Scholar
  6. 6.
    Vesalainen,S., Lipponen,P., Talja,M., & Syrjanen,K. (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. Eur.J.Cancer, 30A, 1797–1803.PubMedGoogle Scholar
  7. 7.
    Naito,Y., Saito,K., Shiiba,K., Ohuchi,A., Saigenji,K., Nagura,H., & Ohtani,H. (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res., 58, 3491–3494.PubMedGoogle Scholar
  8. 8.
    Mortarini,R., Piris,A., Maurichi,A., Molla,A., Bersani,I., Bono,A., Bartoli,C., Santinami,M., Lombardo,C., Ravagnani,F., Cascinelli,N., Parmiani,G., & Anichini,A. (2003) Lack of terminally differentiated tumor-specific CD8+ T cells at tumor site in spite of antitumor immunity to self-antigens in human metastatic melanoma. Cancer Res., 63, 2535–2545.PubMedGoogle Scholar
  9. 9.
    Gabrilovich,D. (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat.Rev.Immunol., 4, 941–952.PubMedGoogle Scholar
  10. 10.
    Furumoto,K., Soares,L., Engleman,E.G., & Merad,M. (2004) Induction of potent antitumor immunity by in situ targeting of intratumoral DCs. J.Clin.Invest, 113, 774–783.PubMedGoogle Scholar
  11. 11.
    Young,J.W. & Inaba,K. (1996) Dendritic cells as adjuvants for class I major histocompatibility complex-restricted antitumor immunity. J.Exp.Med., 183, 7–11.PubMedGoogle Scholar
  12. 12.
    Dranoff,G., Jaffee,E., Lazenby,A., Golumbek,P., Levitsky,H., Brose,K., Jackson,V., Hamada,H., Pardoll,D., & Mulligan,R.C. (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc.Natl.Acad.Sci.U.S.A, 90, 3539–3543.PubMedGoogle Scholar
  13. 13.
    Finn,O.J. (2003) Cancer vaccines: between the idea and the reality. Nat.Rev.Immunol., 3, 630–641.PubMedGoogle Scholar
  14. 14.
    Rosenberg,S.A., Yang,J.C., & Restifo,N.P. (2004) Cancer immunotherapy: moving beyond current vaccines. Nat.Med., 10, 909–915.PubMedGoogle Scholar
  15. 15.
    Rosenberg,S.A., Sherry,R.M., Morton,K.E., Scharfman,W.J., Yang,J.C., Topalian,S.L., Royal,R.E., Kammula,U., Restifo,N.P., Hughes,M.S., Schwartzentruber,D., Berman,D.M., Schwarz,S.L., Ngo,L.T., Mavroukakis,S.A., White,D.E., & Steinberg,S.M. (2005) Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J.Immunol., 175, 6169–6176.PubMedGoogle Scholar
  16. 16.
    Nishikawa,H., Qian,F., Tsuji,T., Ritter,G., Old,L.J., Gnjatic,S., & Odunsi,K. (2006) Influence of CD4+CD25+ regulatory T cells on low/high-avidity CD4+ T cells following peptide vaccination. J.Immunol., 176, 6340–6346.PubMedGoogle Scholar
  17. 17.
    Dhodapkar,M.V., Steinman,R.M., Krasovsky,J., Munz,C., & Bhardwaj,N. (2001) Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J.Exp.Med., 193, 233–238.PubMedGoogle Scholar
  18. 18.
    Chakraborty,N.G., Chattopadhyay,S., Mehrotra,S., Chhabra,A., & Mukherji,B. (2004) Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. Hum.Immunol., 65, 794–802.PubMedGoogle Scholar
  19. 19.
    Thompson,R.H., Gillett,M.D., Cheville,J.C., Lohse,C.M., Dong,H., Webster,W.S., Krejci,K.G., Lobo,J.R., Sengupta,S., Chen,L., Zincke,H., Blute,M.L., Strome,S.E., Leibovich,B.C., & Kwon,E.D. (2004) Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc.Natl.Acad.Sci.U.S.A, 101, 17174–17179.PubMedGoogle Scholar
  20. 20.
    Blank,C., Brown,I., Peterson,A.C., Spiotto,M., Iwai,Y., Honjo,T., & Gajewski,T.F. (2004) PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res., 64, 1140–1145.PubMedGoogle Scholar
  21. 21.
    Harding,F.A., McArthur,J.G., Gross,J.A., Raulet,D.H., & Allison,J.P. (1992) CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature, 356, 607–609.PubMedGoogle Scholar
  22. 22.
    Linsley,P.S., Brady,W., Grosmaire,L., Aruffo,A., Damle,N.K., & Ledbetter,J.A. (1991) Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation. J.Exp.Med., 173, 721–730.PubMedGoogle Scholar
  23. 23.
    Hathcock,K.S., Laszlo,G., Pucillo,C., Linsley,P., & Hodes,R.J. (1994) Comparative analysis of B7–1 and B7–2 costimulatory ligands: expression and function. J.Exp.Med., 180, 631–640.PubMedGoogle Scholar
  24. 24.
    Lenschow,D.J. & Bluestone,J.A. (1993) T cell co-stimulation and in vivo tolerance. Curr.Opin.Immunol., 5, 747–752.PubMedGoogle Scholar
  25. 25.
    Fallarino,F., Grohmann,U., Hwang,K.W., Orabona,C., Vacca,C., Bianchi,R., Belladonna,M.L., Fioretti,M.C., Alegre,M.L., & Puccetti,P. (2003) Modulation of tryptophan catabolism by regulatory T cells. Nat.Immunol., 4, 1206–1212.PubMedGoogle Scholar
  26. 26.
    Shahinian,A., Pfeffer,K., Lee,K.P., Kundig,T.M., Kishihara,K., Wakeham,A., Kawai,K., Ohashi,P.S., Thompson,C.B., & Mak,T.W. (1993) Differential T cell costimulatory requirements in CD28-deficient mice. Science, 261, 609–612.PubMedGoogle Scholar
  27. 27.
    Borriello,F., Sethna,M.P., Boyd,S.D., Schweitzer,A.N., Tivol,E.A., Jacoby,D., Strom,T.B., Simpson,E.M., Freeman,G.J., & Sharpe,A.H. (1997) B7–1 and B7–2 have overlapping, critical roles in immunoglobulin class switching and germinal center formation. Immunity., 6, 303–313.PubMedGoogle Scholar
  28. 28.
    Diehn,M., Alizadeh,A.A., Rando,O.J., Liu,C.L., Stankunas,K., Botstein,D., Crabtree,G.R., & Brown,P.O. (2002) Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation. Proc.Natl.Acad.Sci.U.S.A, 99, 11796–11801.PubMedGoogle Scholar
  29. 29.
    Riley,J.L., Mao,M., Kobayashi,S., Biery,M., Burchard,J., Cavet,G., Gregson,B.P., June,C.H., & Linsley,P.S. (2002) Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors. Proc.Natl.Acad.Sci.U.S.A, 99, 11790–11795.PubMedGoogle Scholar
  30. 30.
    Viola,A. & Lanzavecchia,A. (1996) T cell activation determined by T cell receptor number and tunable thresholds. Science, 273, 104–106.PubMedGoogle Scholar
  31. 31.
    Waterhouse,P., Penninger,J.M., Timms,E., Wakeham,A., Shahinian,A., Lee,K.P., Thompson,C.B., Griesser,H., & Mak,T.W. (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 270, 985–988.PubMedGoogle Scholar
  32. 32.
    Tivol,E.A., Borriello,F., Schweitzer,A.N., Lynch,W.P., Bluestone,J.A., & Sharpe,A.H. (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity., 3, 541–547.PubMedGoogle Scholar
  33. 33.
    Chambers,C.A., Sullivan,T.J., & Allison,J.P. (1997) Lymphoproliferation in CTLA-4-deficient mice is mediated by costimulation-dependent activation of CD4+ T cells. Immunity., 7, 885–895.PubMedGoogle Scholar
  34. 34.
    Blair,P.J., Riley,J.L., Levine,B.L., Lee,K.P., Craighead,N., Francomano,T., Perfetto,S.J., Gray,G.S., Carreno,B.M., & June,C.H. (1998) CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction. J.Immunol., 160, 12–15.PubMedGoogle Scholar
  35. 35.
    Brunner,M.C., Chambers,C.A., Chan,F.K., Hanke,J., Winoto,A., & Allison,J.P. (1999) CTLA-4-Mediated inhibition of early events of T cell proliferation. J.Immunol., 162, 5813–5820.PubMedGoogle Scholar
  36. 36.
    Egen,J.G. & Allison,J.P. (2002) Cytotoxic T lymphocyte antigen-4 accumulation in the immunological synapse is regulated by TCR signal strength. Immunity., 16, 23–35.PubMedGoogle Scholar
  37. 37.
    Shiratori,T., Miyatake,S., Ohno,H., Nakaseko,C., Isono,K., Bonifacino,J.S., & Saito,T. (1997) Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2. Immunity., 6, 583–589.PubMedGoogle Scholar
  38. 38.
    van der Merwe,P.A. & Davis,S.J. (2003) Molecular interactions mediating T cell antigen recognition. Annu.Rev.Immunol., 21, 659–684.PubMedGoogle Scholar
  39. 39.
    Stamper,C.C., Zhang,Y., Tobin,J.F., Erbe,D.V., Ikemizu,S., Davis,S.J., Stahl,M.L., Seehra,J., Somers,W.S., & Mosyak,L. (2001) Crystal structure of the B7–1/CTLA-4 complex that inhibits human immune responses. Nature, 410, 608–611.PubMedGoogle Scholar
  40. 40.
    Greene,J.L., Leytze,G.M., Emswiler,J., Peach,R., Bajorath,J., Cosand,W., & Linsley,P.S. (1996) Covalent dimerization of CD28/CTLA-4 and oligomerization of CD80/CD86 regulate T cell costimulatory interactions. J.Biol.Chem., 271, 26762–26771.PubMedGoogle Scholar
  41. 41.
    Nakaseko,C., Miyatake,S., Iida,T., Hara,S., Abe,R., Ohno,H., Saito,Y., & Saito,T. (1999) Cytotoxic T lymphocyte antigen 4 (CTLA-4) engagement delivers an inhibitory signal through the membrane-proximal region in the absence of the tyrosine motif in the cytoplasmic tail. J.Exp.Med., 190, 765–774.PubMedGoogle Scholar
  42. 42.
    Carreno,B.M., Bennett,F., Chau,T.A., Ling,V., Luxenberg,D., Jussif,J., Baroja,M.L., & Madrenas,J. (2000) CTLA-4 (CD152) can inhibit T cell activation by two different mechanisms depending on its level of cell surface expression. J.Immunol., 165, 1352–1356.PubMedGoogle Scholar
  43. 43.
    Masteller,E.L., Chuang,E., Mullen,A.C., Reiner,S.L., & Thompson,C.B. (2000) Structural analysis of CTLA-4 function in vivo. J.Immunol., 164, 5319–5327.PubMedGoogle Scholar
  44. 44.
    Chikuma,S., Abbas,A.K., & Bluestone,J.A. (2005) B7-independent inhibition of T cells by CTLA-4. J.Immunol., 175, 177–181.PubMedGoogle Scholar
  45. 45.
    Takahashi,S., Kataoka,H., Hara,S., Yokosuka,T., Takase,K., Yamasaki,S., Kobayashi,W., Saito,Y., & Saito,T. (2005) In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection. Eur.J.Immunol., 35, 399–407.PubMedGoogle Scholar
  46. 46.
    Vijayakrishnan,L., Slavik,J.M., Illes,Z., Greenwald,R.J., Rainbow,D., Greve,B., Peterson,L.B., Hafler,D.A., Freeman,G.J., Sharpe,A.H., Wicker,L.S., & Kuchroo,V.K. (2004) An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells. Immunity., 20, 563–575.PubMedGoogle Scholar
  47. 47.
    Chambers,C.A., Sullivan,T.J., Truong,T., & Allison,J.P. (1998) Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells. Eur.J.Immunol., 28, 3137–3143.PubMedGoogle Scholar
  48. 48.
    Chambers,C.A., Kuhns,M.S., & Allison,J.P. (1999) Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4(+) T cell responses. Proc.Natl.Acad.Sci.U.S.A, 96, 8603–8608.PubMedGoogle Scholar
  49. 49.
    Luhder,F., Chambers,C., Allison,J.P., Benoist,C., & Mathis,D. (2000) Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells. Proc.Natl.Acad.Sci.U.S.A, 97, 12204–12209.PubMedGoogle Scholar
  50. 50.
    Greenwald,R.J., Boussiotis,V.A., Lorsbach,R.B., Abbas,A.K., & Sharpe,A.H. (2001) CTLA-4 regulates induction of anergy in vivo. Immunity., 14, 145–155.PubMedGoogle Scholar
  51. 51.
    Probst,H.C., McCoy,K., Okazaki,T., Honjo,T., & van den,B.M. (2005) Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat.Immunol., 6, 280–286.PubMedGoogle Scholar
  52. 52.
    Leach,D.R., Krummel,M.F., & Allison,J.P. (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science, 271, 1734–1736.PubMedGoogle Scholar
  53. 53.
    Yang,Y.F., Zou,J.P., Mu,J., Wijesuriya,R., Ono,S., Walunas,T., Bluestone,J., Fujiwara,H., & Hamaoka,T. (1997) Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages. Cancer Res., 57, 4036–4041.PubMedGoogle Scholar
  54. 54.
    Kwon,E.D., Hurwitz,A.A., Foster,B.A., Madias,C., Feldhaus,A.L., Greenberg,N.M., Burg,M.B., & Allison,J.P. (1997) Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer. Proc.Natl.Acad.Sci.U.S.A, 94, 8099–8103.PubMedGoogle Scholar
  55. 55.
    Shrikant,P., Khoruts,A., & Mescher,M.F. (1999) CTLA-4 blockade reverses CD8+ T cell tolerance to tumor by a CD4+ T cell- and IL-2-dependent mechanism. Immunity., 11, 483–493.PubMedGoogle Scholar
  56. 56.
    Sotomayor,E.M., Borrello,I., Tubb,E., Allison,J.P., & Levitsky,H.I. (1999) In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance. Proc.Natl.Acad.Sci.U.S.A, 96, 11476–11481.PubMedGoogle Scholar
  57. 57.
    van Elsas,A., Hurwitz,A.A., & Allison,J.P. (1999) 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., 190, 355–366.PubMedGoogle Scholar
  58. 58.
    Hurwitz,A.A., Yu,T.F., Leach,D.R., & Allison,J.P. (1998) 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, 95, 10067–10071.PubMedGoogle Scholar
  59. 59.
    Hurwitz,A.A., Foster,B.A., Kwon,E.D., Truong,T., Choi,E.M., Greenberg,N.M., Burg,M.B., & Allison,J.P. (2000) Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade. Cancer Res., 60, 2444–2448.PubMedGoogle Scholar
  60. 60.
    Gregor,P.D., Wolchok,J.D., Ferrone,C.R., Buchinshky,H., Guevara-Patino,J.A., Perales,M.A., Mortazavi,F., Bacich,D., Heston,W., Latouche,J.B., Sadelain,M., Allison,J.P., Scher,H.I., & Houghton,A.N. (2004) 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, 22, 1700–1708.PubMedGoogle Scholar
  61. 61.
    Demaria,S., Kawashima,N., Yang,A.M., Devitt,M.L., Babb,J.S., Allison,J.P., & Formenti,S.C. (2005) Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin.Cancer Res., 11, 728–734.PubMedGoogle Scholar
  62. 62.
    Mokyr,M.B., Kalinichenko,T., Gorelik,L., & Bluestone,J.A. (1998) Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res., 58, 5301–5304.PubMedGoogle Scholar
  63. 63.
    Davila,E., Kennedy,R., & Celis,E. (2003) Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG-oligodeoxynucleotide adjuvant, and CTLA-4 blockade. Cancer Res., 63, 3281–3288.PubMedGoogle Scholar
  64. 64.
    Ko,K., Yamazaki,S., Nakamura,K., Nishioka,T., Hirota,K., Yamaguchi,T., Shimizu,J., Nomura,T., Chiba,T., & Sakaguchi,S. (2005) Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J.Exp.Med., 202, 885–891.PubMedGoogle Scholar
  65. 65.
    Sutmuller,R.P., van Duivenvoorde,L.M., van Elsas,A., Schumacher,T.N., Wildenberg,M.E., Allison,J.P., Toes,R.E., Offringa,R., & Melief,C.J. (2001) Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses. J.Exp.Med., 194, 823–832.PubMedGoogle Scholar
  66. 66.
    Woo,E.Y., Chu,C.S., Goletz,T.J., Schlienger,K., Yeh,H., Coukos,G., Rubin,S.C., Kaiser,L.R., & June,C.H. (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res., 61, 4766–4772.PubMedGoogle Scholar
  67. 67.
    Woo,E.Y., Yeh,H., Chu,C.S., Schlienger,K., Carroll,R.G., Riley,J.L., Kaiser,L.R., & June,C.H. (2002) Cutting edge: Regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J.Immunol., 168, 4272–4276.PubMedGoogle Scholar
  68. 68.
    Liyanage,U.K., Moore,T.T., Joo,H.G., Tanaka,Y., Herrmann,V., Doherty,G., Drebin,J.A., Strasberg,S.M., Eberlein,T.J., Goedegebuure,P.S., & Linehan,D.C. (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J.Immunol., 169, 2756–2761.PubMedGoogle Scholar
  69. 69.
    Curiel,T.J., Coukos,G., Zou,L., Alvarez,X., Cheng,P., Mottram,P., Evdemon-Hogan,M., Conejo-Garcia,J.R., Zhang,L., Burow,M., Zhu,Y., Wei,S., Kryczek,I., Daniel,B., Gordon,A., Myers,L., Lackner,A., Disis,M.L., Knutson,K.L., Chen,L., & Zou,W. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat.Med., 10, 942–949.PubMedGoogle Scholar
  70. 70.
    Viguier,M., Lemaitre,F., Verola,O., Cho,M.S., Gorochov,G., Dubertret,L., Bachelez,H., Kourilsky,P., & Ferradini,L. (2004) Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J.Immunol., 173, 1444–1453.PubMedGoogle Scholar
  71. 71.
    Groux,H., O’Garra,A., Bigler,M., Rouleau,M., Antonenko,S., de Vries,J.E., & Roncarolo,M.G. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature, 389, 737–742.PubMedGoogle Scholar
  72. 72.
    Levings,M.K., Sangregorio,R., Galbiati,F., Squadrone,S., de Waal,M.R., & Roncarolo,M.G. (2001a) IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J.Immunol., 166, 5530–5539.Google Scholar
  73. 73.
    Weiner,H.L. (2001) Induction and mechanism of action of transforming growth factor-beta-secreting Th3 regulatory cells. Immunol.Rev., 182, 207–214.PubMedGoogle Scholar
  74. 74.
    Walker,M.R., Kasprowicz,D.J., Gersuk,V.H., Benard,A., Van Landeghen,M., Buckner,J.H., & Ziegler,S.F. (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+. J.Clin.Invest, 112, 1437–1443.PubMedGoogle Scholar
  75. 75.
    Chen,W., Jin,W., Hardegen,N., Lei,K.J., Li,L., Marinos,N., McGrady,G., & Wahl,S.M. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J.Exp.Med., 198, 1875–1886.PubMedGoogle Scholar
  76. 76.
    Apostolou,I. & von Boehmer,H. (2004) In vivo instruction of suppressor commitment in naive T cells. J.Exp.Med., 199, 1401–1408.PubMedGoogle Scholar
  77. 77.
    Kretschmer,K., Apostolou,I., Hawiger,D., Khazaie,K., Nussenzweig,M.C., & von Boehmer,H. (2005) Inducing and expanding regulatory T cell populations by foreign antigen. Nat.Immunol., 6, 1219–1227.PubMedGoogle Scholar
  78. 78.
    Curotto de Lafaille,M.A., Lino,A.C., Kutchukhidze,N., & Lafaille,J.J. (2004) CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J.Immunol., 173, 7259–7268.PubMedGoogle Scholar
  79. 79.
    Zhou,G., Drake,C.G., & Levitsky,H.I. (2005) Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood.Google Scholar
  80. 80.
    Gilliet,M. & Liu,Y.J. (2002) Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J.Exp.Med., 195, 695–704.PubMedGoogle Scholar
  81. 81.
    Zheng,S.G., Wang,J.H., Koss,M.N., Quismorio,F., Jr., Gray,J.D., & Horwitz,D.A. (2004) CD4+ and CD8+ regulatory T cells generated ex vivo with IL-2 and TGF-beta suppress a stimulatory graft-versus-host disease with a lupus-like syndrome. J.Immunol., 172, 1531–1539.PubMedGoogle Scholar
  82. 82.
    Chang,C.C., Ciubotariu,R., Manavalan,J.S., Yuan,J., Colovai,A.I., Piazza,F., Lederman,S., Colonna,M., Cortesini,R., Dalla-Favera,R., & Suciu-Foca,N. (2002) Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat.Immunol., 3, 237–243.PubMedGoogle Scholar
  83. 83.
    Noble,A., Giorgini,A., & Leggat,J.A. (2006) Cytokine-induced IL-10-secreting CD8 T cells represent a phenotypically distinct suppressor T-cell lineage. Blood, 107, 4475–4483.PubMedGoogle Scholar
  84. 84.
    Shimizu,J., Yamazaki,S., & Sakaguchi,S. (1999) Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J.Immunol., 163, 5211–5218.PubMedGoogle Scholar
  85. 85.
    Marshall,N.A., Christie,L.E., Munro,L.R., Culligan,D.J., Johnston,P.W., Barker,R.N., & Vickers,M.A. (2004) Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood, 103, 1755–1762.PubMedGoogle Scholar
  86. 86.
    Alvaro,T., Lejeune,M., Salvado,M.T., Bosch,R., Garcia,J.F., Jaen,J., Banham,A.H., Roncador,G., Montalban,C., & Piris,M.A. (2005) Outcome in Hodgkin’s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin.Cancer Res., 11, 1467–1473.PubMedGoogle Scholar
  87. 87.
    Dave,S.S., Wright,G., Tan,B., Rosenwald,A., Gascoyne,R.D., Chan,W.C., Fisher,R.I., Braziel,R.M., Rimsza,L.M., Grogan,T.M., Miller,T.P., LeBlanc,M., Greiner,T.C., Weisenburger,D.D., Lynch,J.C., Vose,J., Armitage,J.O., Smeland,E.B., Kvaloy,S., Holte,H., Delabie,J., Connors,J.M., Lansdorp,P.M., Ouyang,Q., Lister,T.A., Davies,A.J., Norton,A.J., Muller-Hermelink,H.K., Ott,G., Campo,E., Montserrat,E., Wilson,W.H., Jaffe,E.S., Simon,R., Yang,L., Powell,J., Zhao,H., Goldschmidt,N., Chiorazzi,M., & Staudt,L.M. (2004) Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. N.Engl.J.Med., 351, 2159–2169.PubMedGoogle Scholar
  88. 88.
    Furtado,G.C., Curotto de Lafaille,M.A., Kutchukhidze,N., & Lafaille,J.J. (2002) Interleukin 2 signaling is required for CD4(+) regulatory T cell function. J.Exp.Med., 196, 851–857.PubMedGoogle Scholar
  89. 89.
    Almeida,A.R., Legrand,N., Papiernik,M., & Freitas,A.A. (2002) Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers. J.Immunol., 169, 4850–4860.PubMedGoogle Scholar
  90. 90.
    Malek,T.R. & Bayer,A.L. (2004) Tolerance, not immunity, crucially depends on IL-2. Nat.Rev.Immunol., 4, 665–674.PubMedGoogle Scholar
  91. 91.
    Zhang,H., Chua,K.S., Guimond,M., Kapoor,V., Brown,M.V., Fleisher,T.A., Long,L.M., Bernstein,D., Hill,B.J., Douek,D.C., Berzofsky,J.A., Carter,C.S., Read,E.J., Helman,L.J., & Mackall,C.L. (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat.Med., 11, 1238–1243.PubMedGoogle Scholar
  92. 92.
    Ahmadzadeh,M. & Rosenberg,S.A. (2006) IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood, 107, 2409–2414.PubMedGoogle Scholar
  93. 93.
    Zou,W. (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat.Rev.Immunol., 6, 295–307.PubMedGoogle Scholar
  94. 94.
    Zhou,G., Drake,C.G., & Levitsky,H.I. (2006) Amplification of tumor-specific regulatory T cells following therapeutic cancer vaccines. Blood, 107, 628–636.PubMedGoogle Scholar
  95. 95.
    Yamazaki,S., Iyoda,T., Tarbell,K., Olson,K., Velinzon,K., Inaba,K., & Steinman,R.M. (2003) Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells. J.Exp.Med., 198, 235–247.PubMedGoogle Scholar
  96. 96.
    Thornton,A.M. & Shevach,E.M. (2000) Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J.Immunol., 164, 183–190.PubMedGoogle Scholar
  97. 97.
    Piccirillo,C.A., Letterio,J.J., Thornton,A.M., McHugh,R.S., Mamura,M., Mizuhara,H., & Shevach,E.M. (2002) CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J.Exp.Med., 196, 237–246.PubMedGoogle Scholar
  98. 98.
    Stephens,L.A., Mottet,C., Mason,D., & Powrie,F. (2001) Human CD4(+)CD25(+) thymocytes and peripheral T cells have immune suppressive activity in vitro. Eur.J.Immunol., 31, 1247–1254.PubMedGoogle Scholar
  99. 99.
    Asseman,C., Mauze,S., Leach,M.W., Coffman,R.L., & Powrie,F. (1999) An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J.Exp.Med., 190, 995–1004.PubMedGoogle Scholar
  100. 100.
    Suri-Payer,E. & Cantor,H. (2001) Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells. J.Autoimmun., 16, 115–123.PubMedGoogle Scholar
  101. 101.
    Chen,M.L., Pittet,M.J., Gorelik,L., Flavell,R.A., Weissleder,R., von Boehmer,H., & Khazaie,K. (2005) Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-beta signals in vivo. Proc.Natl.Acad.Sci.U.S.A, 102, 419–424.PubMedGoogle Scholar
  102. 102.
    Green,E.A., Gorelik,L., McGregor,C.M., Tran,E.H., & Flavell,R.A. (2003) CD4+CD25+ T regulatory cells control anti-islet CD8+ T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc.Natl.Acad.Sci.U.S.A, 100, 10878–10883.PubMedGoogle Scholar
  103. 103.
    Fahlen,L., Read,S., Gorelik,L., Hurst,S.D., Coffman,R.L., Flavell,R.A., & Powrie,F. (2005) T cells that cannot respond to TGF-beta escape control by CD4+CD25+ regulatory T cells. J.Exp.Med., 201, 737–746.PubMedGoogle Scholar
  104. 104.
    Read,S., Malmstrom,V., & Powrie,F. (2000) 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., 192, 295–302.PubMedGoogle Scholar
  105. 105.
    Takahashi,T., Tagami,T., Yamazaki,S., Uede,T., Shimizu,J., Sakaguchi,N., Mak,T.W., & Sakaguchi,S. (2000) Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J.Exp.Med., 192, 303–310.PubMedGoogle Scholar
  106. 106.
    Bachmann,M.F., Kohler,G., Ecabert,B., Mak,T.W., & Kopf,M. (1999) Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J.Immunol., 163, 1128–1131.PubMedGoogle Scholar
  107. 107.
    Kataoka,H., Takahashi,S., Takase,K., Yamasaki,S., Yokosuka,T., Koike,T., & Saito,T. (2005) CD25(+)CD4(+) regulatory T cells exert in vitro suppressive activity independent of CTLA-4. Int.Immunol., 17, 421–427.PubMedGoogle Scholar
  108. 108.
    Tang,Q., Boden,E.K., Henriksen,K.J., Bour-Jordan,H., Bi,M., & Bluestone,J.A. (2004) Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function. Eur.J.Immunol., 34, 2996–3005.PubMedGoogle Scholar
  109. 109.
    Quezada,S.A., Peggs,K.S., Curran,M.A., & Allison,J.P. (2006) CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J.Clin.Invest, 116, 1935–1945.PubMedGoogle Scholar
  110. 109.
    Thornton,A.M. & Shevach,E.M. (1998) CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J.Exp.Med., 188, 287–296.PubMedGoogle Scholar
  111. 110.
    Chai,J.G., Tsang,J.Y., Lechler,R., Simpson,E., Dyson,J., & Scott,D. (2002) CD4+CD25+ T cells as immunoregulatory T cells in vitro. Eur.J.Immunol., 32, 2365–2375.PubMedGoogle Scholar
  112. 111.
    Levings,M.K., Sangregorio,R., & Roncarolo,M.G. (2001b) Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J.Exp.Med., 193, 1295–1302.Google Scholar
  113. 112.
    Annunziato,F., Cosmi,L., Liotta,F., Lazzeri,E., Manetti,R., Vanini,V., Romagnani,P., Maggi,E., & Romagnani,S. (2002) Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J.Exp.Med., 196, 379–387.PubMedGoogle Scholar
  114. 113.
    Paust,S., Lu,L., McCarty,N., & Cantor,H. (2004) Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc.Natl.Acad.Sci.U.S.A, 101, 10398–10403.PubMedGoogle Scholar
  115. 114.
    Taylor,P.A., Lees,C.J., Fournier,S., Allison,J.P., Sharpe,A.H., & Blazar,B.R. (2004) B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via T-T interactions [corrections]. J.Immunol., 172, 34–39.PubMedGoogle Scholar
  116. 115.
    Shevach,E.M. (2002) CD4+ CD25+ suppressor T cells: more questions than answers. Nat.Rev.Immunol., 2, 389–400.PubMedGoogle Scholar
  117. 116.
    Malek,T.R., Yu,A., Vincek,V., Scibelli,P., & Kong,L. (2002) CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity., 17, 167–178.PubMedGoogle Scholar
  118. 117.
    Onizuka,S., Tawara,I., Shimizu,J., Sakaguchi,S., Fujita,T., & Nakayama,E. (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res., 59, 3128–3133.PubMedGoogle Scholar
  119. 118.
    Steitz,J., Bruck,J., Lenz,J., Knop,J., & Tuting,T. (2001) Depletion of CD25(+) CD4(+) T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the interferon alpha-induced, CD8(+) T-cell-dependent immune defense of B16 melanoma. Cancer Res., 61, 8643–8646.PubMedGoogle Scholar
  120. 119.
    Nagai,H., Horikawa,T., Hara,I., Fukunaga,A., Oniki,S., Oka,M., Nishigori,C., & Ichihashi,M. (2004) In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with interleukin-12 gene transfer. Exp.Dermatol., 13, 613–620.PubMedGoogle Scholar
  121. 120.
    Prasad,S.J., Farrand,K.J., Matthews,S.A., Chang,J.H., McHugh,R.S., & Ronchese,F. (2005) Dendritic cells loaded with stressed tumor cells elicit long-lasting protective tumor immunity in mice depleted of CD4+CD25+ regulatory T cells. J.Immunol., 174, 90–98.PubMedGoogle Scholar
  122. 121.
    Dannull,J., Su,Z., Rizzieri,D., Yang,B.K., Coleman,D., Yancey,D., Zhang,A., Dahm,P., Chao,N., Gilboa,E., & Vieweg,J. (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J.Clin.Invest, 115, 3623–3633.PubMedGoogle Scholar
  123. 122.
    Barnett,B., Kryczek,I., Cheng,P., Zou,W., & Curiel,T.J. (2005) Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am.J.Reprod.Immunol., 54, 369–377.PubMedGoogle Scholar
  124. 123.
    Antony,P.A., Piccirillo,C.A., Akpinarli,A., Finkelstein,S.E., Speiss,P.J., Surman,D.R., Palmer,D.C., Chan,C.C., Klebanoff,C.A., Overwijk,W.W., Rosenberg,S.A., & Restifo,N.P. (2005) CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J.Immunol., 174, 2591–2601.PubMedGoogle Scholar
  125. 124.
    Gattinoni,L., Powell,D.J., Jr., Rosenberg,S.A., & Restifo,N.P. (2006) Adoptive immunotherapy for cancer: building on success. Nat.Rev.Immunol., 6, 383–393.PubMedGoogle Scholar
  126. 125.
    Turk,M.J., Guevara-Patino,J.A., Rizzuto,G.A., Engelhorn,M.E., Sakaguchi,S., & Houghton,A.N. (2004) Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J.Exp.Med., 200, 771–782.PubMedGoogle Scholar
  127. 126.
    Cohen,A.D., Diab,A., Perales,M.A., Wolchok,J.D., Rizzuto,G., Merghoub,T., Huggins,D., Liu,C., Turk,M.J., Restifo,N.P., Sakaguchi,S., & Houghton,A.N. (2006) Agonist anti-GITR antibody enhances vaccine-induced CD8(+) T-cell responses and tumor immunity. Cancer Res., 66, 4904–4912.PubMedGoogle Scholar
  128. 127.
    Sugamura,K., Ishii,N., & Weinberg,A.D. (2004) Therapeutic targeting of the effector T-cell co-stimulatory molecule OX40. Nat.Rev.Immunol., 4, 420–431.PubMedGoogle Scholar
  129. 128.
    Shimizu,J., Yamazaki,S., Takahashi,T., Ishida,Y., & Sakaguchi,S. (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat.Immunol., 3, 135–142.PubMedGoogle Scholar
  130. 129.
    Valzasina,B., Guiducci,C., Dislich,H., Killeen,N., Weinberg,A.D., & Colombo,M.P. (2005) 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, 105, 2845–2851.PubMedGoogle Scholar
  131. 130.
    Stephens,G.L., McHugh,R.S., Whitters,M.J., Young,D.A., Luxenberg,D., Carreno,B.M., Collins,M., & Shevach,E.M. (2004) 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., 173, 5008–5020.PubMedGoogle Scholar
  132. 131.
    Hodi,F.S. & Dranoff,G. (2006) Combinatorial cancer immunotherapy. Adv.Immunol., 90, 341–368.PubMedGoogle Scholar
  133. 132.
    Phan,G.Q., Yang,J.C., Sherry,R.M., Hwu,P., Topalian,S.L., Schwartzentruber,D.J., Restifo,N.P., Haworth,L.R., Seipp,C.A., Freezer,L.J., Morton,K.E., Mavroukakis,S.A., Duray,P.H., Steinberg,S.M., Allison,J.P., Davis,T.A., & Rosenberg,S.A. (2003) 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, 100, 8372–8377.PubMedGoogle Scholar
  134. 133.
    Hodi,F.S., Mihm,M.C., Soiffer,R.J., Haluska,F.G., Butler,M., Seiden,M.V., Davis,T., Henry-Spires,R., MacRae,S., Willman,A., Padera,R., Jaklitsch,M.T., Shankar,S., Chen,T.C., Korman,A., Allison,J.P., & Dranoff,G. (2003) 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, 100, 4712–4717.PubMedGoogle Scholar
  135. 134.
    Attia,P., Phan,G.Q., Maker,A.V., Robinson,M.R., Quezado,M.M., Yang,J.C., Sherry,R.M., Topalian,S.L., Kammula,U.S., Royal,R.E., Restifo,N.P., Haworth,L.R., Levy,C., Mavroukakis,S.A., Nichol,G., Yellin,M.J., & Rosenberg,S.A. (2005) Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J.Clin.Oncol., 23, 6043–6053.PubMedGoogle Scholar
  136. 135.
    Sanderson,K., Scotland,R., Lee,P., Liu,D., Groshen,S., Snively,J., Sian,S., Nichol,G., Davis,T., Keler,T., Yellin,M., & Weber,J. (2005) 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., 23, 741–750.PubMedGoogle Scholar
  137. 136.
    Ribas,A., Camacho,L.H., Lopez-Berestein,G., Pavlov,D., Bulanhagui,C.A., Millham,R., Comin-Anduix,B., Reuben,J.M., Seja,E., Parker,C.A., Sharma,A., Glaspy,J.A., & Gomez-Navarro,J. (2005) 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., 23, 8968–8977.PubMedGoogle Scholar
  138. 137.
    Beck,K.E., Blansfield,J.A., Tran,K.Q., Feldman,A.L., Hughes,M.S., Royal,R.E., Kammula,U.S., Topalian,S.L., Sherry,R.M., Kleiner,D., Quezado,M., Lowy,I., Yellin,M., Rosenberg,S.A., & Yang,J.C. (2006) Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J.Clin.Oncol., 24, 2283–2289.PubMedGoogle Scholar
  139. 138.
    Peggs,K.S., Quezada,S.A., Korman,A.J., & Allison,J.P. (2006) Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr.Opin.Immunol., 18, 206–213.PubMedGoogle Scholar
  140. 139.
    Lurquin,C., Lethe,B., De Plaen,E., Corbiere,V., Theate,I., van Baren,N., Coulie,P.G., & Boon,T. (2005) Contrasting frequencies of antitumor and anti-vaccine T cells in metastases of a melanoma patient vaccinated with a MAGE tumor antigen. J.Exp.Med., 201, 249–257.PubMedGoogle Scholar
  141. 140.
    Maker,A.V., Phan,G.Q., Attia,P., Yang,J.C., Sherry,R.M., Topalian,S.L., Kammula,U.S., Royal,R.E., Haworth,L.R., Levy,C., Kleiner,D., Mavroukakis,S.A., Yellin,M., & Rosenberg,S.A. (2005) 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., 12, 1005–1016.PubMedGoogle Scholar
  142. 141.
    Atkins,M.B., Lotze,M.T., Dutcher,J.P., Fisher,R.I., Weiss,G., Margolin,K., Abrams,J., Sznol,M., Parkinson,D., Hawkins,M., Paradise,C., Kunkel,L., & Rosenberg,S.A. (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J.Clin.Oncol., 17, 2105–2116.PubMedGoogle Scholar
  143. 142.
    Rosenberg,S.A. (2000) Interleukin-2 and the development of immunotherapy for the treatment of patients with cancer. Cancer J.Sci.Am., 6 Suppl 1, S2-S7.PubMedGoogle Scholar
  144. 143.
    Fong,L., Kavanagh,B., Rini,B.I., Shaw,V., Weinberg,V., & Small,E.J. (2006) A phase I trial of combination immunotherapy with CTLA-4 blockade and GM-CSF in hormone-refractory prostate cancer. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings, 24, 2508.Google Scholar
  145. 144.
    Hurwitz,A.A., Sullivan,T.J., Krummel,M.F., Sobel,R.A., & Allison,J.P. (1997) Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis. J.Neuroimmunol., 73, 57–62.PubMedGoogle Scholar
  146. 145.
    Karandikar,N.J., Vanderlugt,C.L., Walunas,T.L., Miller,S.D., & Bluestone,J.A. (1996) CTLA-4: a negative regulator of autoimmune disease. J.Exp.Med., 184, 783–788.PubMedGoogle Scholar
  147. 146.
    Perrin,P.J., Maldonado,J.H., Davis,T.A., June,C.H., & Racke,M.K. (1996) CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis. J.Immunol., 157, 1333–1336.PubMedGoogle Scholar
  148. 147.
    Luhder,F., Hoglund,P., Allison,J.P., Benoist,C., & Mathis,D. (1998) Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulates the unfolding of autoimmune diabetes. J.Exp.Med., 187, 427–432.PubMedGoogle Scholar
  149. 148.
    Wang,H.B., Shi,F.D., Li,H., Chambers,B.J., Link,H., & Ljunggren,H.G. (2001) Anti-CTLA-4 antibody treatment triggers determinant spreading and enhances murine myasthenia gravis. J.Immunol., 166, 6430–6436.PubMedGoogle Scholar
  150. 149.
    Keler,T., Halk,E., Vitale,L., O’Neill,T., Blanset,D., Lee,S., Srinivasan,M., Graziano,R.F., Davis,T., Lonberg,N., & Korman,A. (2003) Activity and safety of CTLA-4 blockade combined with vaccines in cynomolgus macaques. J.Immunol., 171, 6251–6259.PubMedGoogle Scholar
  151. 150.
    Korman,A., Yellin,M., & Keler,T. (2005) Tumor immunotherapy: preclinical and clinical activity of anti-CTLA4 antibodies. Curr.Opin.Investig.Drugs, 6, 582–591.PubMedGoogle Scholar
  152. 151.
    Robinson,M.R., Chan,C.C., Yang,J.C., Rubin,B.I., Gracia,G.J., Sen,H.N., Csaky,K.G., & Rosenberg,S.A. (2004) Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis. J.Immunother., 27, 478–479.PubMedGoogle Scholar
  153. 152.
    Blansfield,J.A., Beck,K.E., Tran,K., Yang,J.C., Hughes,M.S., Kammula,U.S., Royal,R.E., Topalian,S.L., Haworth,L.R., Levy,C., Rosenberg,S.A., & Sherry,R.M. (2005) Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J.Immunother., 28, 593–598.PubMedGoogle Scholar
  154. 153.
    Dong,H., Strome,S.E., Salomao,D.R., Tamura,H., Hirano,F., Flies,D.B., Roche,P.C., Lu,J., Zhu,G., Tamada,K., Lennon,V.A., Celis,E., & Chen,L. (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat.Med., 8, 793–800.PubMedGoogle Scholar
  155. 154.
    Brown,J.A., Dorfman,D.M., Ma,F.R., Sullivan,E.L., Munoz,O., Wood,C.R., Greenfield,E.A., & Freeman,G.J. (2003) Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J.Immunol., 170, 1257–1266.PubMedGoogle Scholar
  156. 155.
    Ohigashi,Y., Sho,M., Yamada,Y., Tsurui,Y., Hamada,K., Ikeda,N., Mizuno,T., Yoriki,R., Kashizuka,H., Yane,K., Tsushima,F., Otsuki,N., Yagita,H., Azuma,M., & Nakajima,Y. (2005) Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin.Cancer Res., 11, 2947–2953.PubMedGoogle Scholar
  157. 156.
    Rosenwald,A., Wright,G., Leroy,K., Yu,X., Gaulard,P., Gascoyne,R.D., Chan,W.C., Zhao,T., Haioun,C., Greiner,T.C., Weisenburger,D.D., Lynch,J.C., Vose,J., Armitage,J.O., Smeland,E.B., Kvaloy,S., Holte,H., Delabie,J., Campo,E., Montserrat,E., Lopez-Guillermo,A., Ott,G., Muller-Hermelink,H.K., Connors,J.M., Braziel,R., Grogan,T.M., Fisher,R.I., Miller,T.P., LeBlanc,M., Chiorazzi,M., Zhao,H., Yang,L., Powell,J., Wilson,W.H., Jaffe,E.S., Simon,R., Klausner,R.D., & Staudt,L.M. (2003) 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., 198, 851–862.PubMedGoogle Scholar
  158. 157.
    Iwai,Y., Ishida,M., Tanaka,Y., Okazaki,T., Honjo,T., & Minato,N. (2002) 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, 99, 12293–12297.PubMedGoogle Scholar
  159. 158.
    Strome,S.E., Dong,H., Tamura,H., Voss,S.G., Flies,D.B., Tamada,K., Salomao,D., Cheville,J., Hirano,F., Lin,W., Kasperbauer,J.L., Ballman,K.V., & Chen,L. (2003) B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res., 63, 6501–6505.PubMedGoogle Scholar
  160. 159.
    Curiel,T.J., Wei,S., Dong,H., Alvarez,X., Cheng,P., Mottram,P., Krzysiek,R., Knutson,K.L., Daniel,B., Zimmermann,M.C., David,O., Burow,M., Gordon,A., Dhurandhar,N., Myers,L., Berggren,R., Hemminki,A., Alvarez,R.D., Emilie,D., Curiel,D.T., Chen,L., & Zou,W. (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat.Med., 9, 562–567.PubMedGoogle Scholar
  161. 160.
    Carter,L., Fouser,L.A., Jussif,J., Fitz,L., Deng,B., Wood,C.R., Collins,M., Honjo,T., Freeman,G.J., & Carreno,B.M. (2002) PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur.J.Immunol., 32, 634–643.PubMedGoogle Scholar
  162. 161.
    Liu,X., Gao,J.X., Wen,J., Yin,L., Li,O., Zuo,T., Gajewski,T.F., Fu,Y.X., Zheng,P., & Liu,Y. (2003) B7DC/PDL2 promotes tumor immunity by a PD-1-independent mechanism. J.Exp.Med., 197, 1721–1730.PubMedGoogle Scholar
  163. 162.
    Iwai,Y., Terawaki,S., & Honjo,T. (2005) PD-1 blockade inhibits hematogenous spread of poorly immunogenic tumor cells by enhanced recruitment of effector T cells. Int.Immunol., 17, 133–144.PubMedGoogle Scholar
  164. 163.
    Suh,W.K., Gajewska,B.U., Okada,H., Gronski,M.A., Bertram,E.M., Dawicki,W., Duncan,G.S., Bukczynski,J., Plyte,S., Elia,A., Wakeham,A., Itie,A., Chung,S., Da Costa,J., Arya,S., Horan,T., Campbell,P., Gaida,K., Ohashi,P.S., Watts,T.H., Yoshinaga,S.K., Bray,M.R., Jordana,M., & Mak,T.W. (2003) The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat.Immunol., 4, 899–906.PubMedGoogle Scholar
  165. 164.
    Zang,X., Loke,P., Kim,J., Murphy,K., Waitz,R., & Allison,J.P. (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc.Natl.Acad.Sci.U.S.A, 100, 10388–10392.PubMedGoogle Scholar
  166. 165.
    Prasad,D.V., Richards,S., Mai,X.M., & Dong,C. (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity., 18, 863–873.PubMedGoogle Scholar
  167. 166.
    Sica,G.L., Choi,I.H., Zhu,G., Tamada,K., Wang,S.D., Tamura,H., Chapoval,A.I., Flies,D.B., Bajorath,J., & Chen,L. (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity., 18, 849–861.PubMedGoogle Scholar
  168. 167.
    Choi,I.H., Zhu,G., Sica,G.L., Strome,S.E., Cheville,J.C., Lau,J.S., Zhu,Y., Flies,D.B., Tamada,K., & Chen,L. (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J.Immunol., 171, 4650–4654.PubMedGoogle Scholar
  169. 168.
    Salceda,S., Tang,T., Kmet,M., Munteanu,A., Ghosh,M., Macina,R., Liu,W., Pilkington,G., & Papkoff,J. (2005) The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp.Cell Res., 306, 128–141.PubMedGoogle Scholar
  170. 169.
    Tringler,B., Zhuo,S., Pilkington,G., Torkko,K.C., Singh,M., Lucia,M.S., Heinz,D.E., Papkoff,J., & Shroyer,K.R. (2005) B7-h4 is highly expressed in ductal and lobular breast cancer. Clin.Cancer Res., 11, 1842–1848.PubMedGoogle Scholar
  171. 170.
    Kryczek,I., Wei,S., Zou,L., Zhu,G., Mottram,P., Xu,H., Chen,L., & Zou,W. (2006a) Cutting Edge: Induction of B7-H4 on APCs through IL-10: Novel Suppressive Mode for Regulatory T Cells. J.Immunol., 177, 40–44.Google Scholar
  172. 171.
    Kryczek,I., Zou,L., Rodriguez,P., Zhu,G., Wei,S., Mottram,P., Brumlik,M., Cheng,P., Curiel,T., Myers,L., Lackner,A., Alvarez,X., Ochoa,A., Chen,L., & Zou,W. (2006b) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J.Exp.Med., 203, 871–881.Google Scholar
  173. 172.
    Han,P., Goularte,O.D., Rufner,K., Wilkinson,B., & Kaye,J. (2004) An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. J.Immunol., 172, 5931–5939.PubMedGoogle Scholar
  174. 173.
    Hurchla,M.A., Sedy,J.R., Gavrielli,M., Drake,C.G., Murphy,T.L., & Murphy,K.M. (2005) B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells. J.Immunol., 174, 3377–3385.PubMedGoogle Scholar
  175. 174.
    Sedy,J.R., Gavrieli,M., Potter,K.G., Hurchla,M.A., Lindsley,R.C., Hildner,K., Scheu,S., Pfeffer,K., Ware,C.F., Murphy,T.L., & Murphy,K.M. (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat.Immunol., 6, 90–98.PubMedGoogle Scholar
  176. 175.
    Gri,G., Gallo,E., Di Carlo,E., Musiani,P., & Colombo,M.P. (2003) 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., 170, 99–106.PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Karl S. Peggs
    • 1
  • Sergio A. Quezada
    • 1
  • James P. Allison
    • 1
  1. 1.Howard Hughes Medical Institute, Department of ImmunologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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