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Current and Future Role of Natural-Killer Cells in Cancer Immunotherapy

  • Chapter
Immunotherapy of Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Natural-killer (NK) cells are a class of lymphocytes distinct in their ability to identify and kill transformed self-cells without priming. Recognition is via receptors that bind unique but common surface molecules induced on these cells. These properties characterize NK cells as unique effectors for use in immunotherapy. Discussed here are past and current experiments and clinical trials geared toward enhancing NK cell cytotoxicity in three general ways:

  1. 1.

    Modification of the NK cell to activate or enhance cytolytic activity.

  2. 2.

    Modification of the tumor to make it more readily identified and more immunogenic.

  3. 3.

    Modification of other immune cells to affect indirectly NK cell activity or to elicit a cooperative effect with both an innate and adaptive immune response.

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References

  1. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop 1991; 262: 3–11.

    PubMed  Google Scholar 

  2. Dunn GP, Old LJ, Schreiber RD. The immunobiology of cancer immunosurveillance and immunoediting. Immunity 2004; 21:137–148.

    Article  PubMed  CAS  Google Scholar 

  3. Raulet DH. Natural killer cells. In: Paul WE, ed. Fundamental Immunology. Philadelphia: Lippincott-Raven. 1999: pp. 365–391.

    Google Scholar 

  4. Raulet DH. Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol 2004; 5:996–1002.

    Article  PubMed  CAS  Google Scholar 

  5. Lanier LL, Le AM, Phillips JH, Warner NL, Babcock GF. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 1983; 131:1789–1796.

    PubMed  CAS  Google Scholar 

  6. Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res 2003; 90:127–156.

    PubMed  CAS  Google Scholar 

  7. Jiang K, Zhong B, Gilvary DL, et al. Syk regulation of phosphoinositide 3-kinase-dependent NK cell function. J Immunol 2002; 168:3155–3164.

    PubMed  CAS  Google Scholar 

  8. Djeu JY, Jiang K, Wei S. A view to a kill: signals triggering cytotoxicity. Clin Cancer Res 2002; 8:636–640.

    PubMed  CAS  Google Scholar 

  9. Jiang K, Zhong B, Gilvary DL, et al. Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells. Nat Immunol 2000; 1:419–425.

    Article  PubMed  CAS  Google Scholar 

  10. Geldhof AB, Van Ginderachter JA, Liu Y, Noel W, Raes G, De Baetselier P. Antagonistic effect of NK cells on alternatively activated monocytes: a contribution of NK cells to CTL generation. Blood 2002; 100:4049–4058.

    Article  PubMed  CAS  Google Scholar 

  11. Smyth MJ, Crowe NY, Godfrey DI. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 2001; 13:459–463.

    Article  PubMed  CAS  Google Scholar 

  12. Crowe NY, Smyth MJ, Godfrey DI. A critical role for natural killer T cells in immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med 2002; 196:119–127.

    Article  PubMed  CAS  Google Scholar 

  13. van den Broeke LT, Daschbach E, Thomas EK, Andringa G, Berzofsky JA. Dendritic cell-induced activation of adaptive and innate antitumor immunity. J Immunol 2003; 171:5842–5852.

    PubMed  Google Scholar 

  14. Kagi D, Ledermann B, Burki K, et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 1994; 369:31–37.

    Article  PubMed  CAS  Google Scholar 

  15. Redondo M, Garcia J, Villar E, et al. Major histocompatibility complex status in breast carcinogenesis and relationship to apoptosis. Hum Pathol 2003; 34:1283–1289.

    Article  PubMed  CAS  Google Scholar 

  16. Agrawal S, Kishore MC. MHC class I gene expression and regulation. J Hematother Stem Cell Res 2000; 9:795–812.

    Article  PubMed  CAS  Google Scholar 

  17. Atkins D, Ferrone S, Schmahl GE, Storkel S, Seliger B. Down-regulation of HLA class I antigen processing molecules: an immune escape mechanism of renal cell carcinoma? J Urol 2004; 171(Pt 1):885–889.

    Article  PubMed  CAS  Google Scholar 

  18. Vitale M, Rezzani R, Rodella L, et al. HLA class I antigen and transporter associated with antigen processing (TAP1 and TAP2) down-regulation in high-grade primary breast carcinoma lesions. Cancer Res 1998; 58:737–742.

    PubMed  CAS  Google Scholar 

  19. Parham P, McQueen KL. Alloreactive killer cells: hindrance and help for haematopoietic transplants. Nat Rev Immunol 2003; 3:108–122.

    Article  PubMed  CAS  Google Scholar 

  20. Ruggeri L, Capanni M, Martelli MF, Velardi A. Cellular therapy: exploiting NK cell alloreactivity in transplantation. Curr Opin Hematol 2001; 8:355–359.

    Article  PubMed  CAS  Google Scholar 

  21. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 1982; 155:1823–1841.

    Article  PubMed  CAS  Google Scholar 

  22. Grimm EA, Jacobs SK, Lanza LA, Melin G, Roth JA, Wilson DJ. Interleukin 2-activated cytotoxic lymphocytes in cancer therapy. Symp Fundam Cancer Res 1986; 38:209–219.

    PubMed  CAS  Google Scholar 

  23. Phillips JH, Lanier LL. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 1986; 164:814–825.

    Article  PubMed  CAS  Google Scholar 

  24. Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 313:1485–1492.

    Article  PubMed  CAS  Google Scholar 

  25. Ahlberg R, MacNamara B, Andersson M, et al. Stimulation of T-cell cytokine production and NK cell function by IL-2, IFN-alpha and histamine treatment during remission of non-Hodgkin’s lymphoma. Hematol J 2003; 4:336–341.

    Article  PubMed  CAS  Google Scholar 

  26. Lehmann C, Zeis M, Uharek L. Activation of natural killer cells with interleukin 2 (IL-2) and IL-12 increases perforin binding and subsequent lysis of tumour cells. Br J Haematol 2001; 114:660–665.

    Article  PubMed  CAS  Google Scholar 

  27. Xiang J, Chen Z, Huang H, Moyana T. Regression of engineered myeloma cells secreting interferongamma-inducing factor is mediated by both CD4(+)/CD8(+) T and natural killer cells. Leuk Res 2001; 25:909–915.

    Article  PubMed  CAS  Google Scholar 

  28. Wang G, Tschoi M, Spolski R, et al. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Cancer Res 2003; 63:9016–9022.

    PubMed  CAS  Google Scholar 

  29. Lum JJ, Schnepple DJ, Nie Z, et al. Differential effects of interleukin-7 and interleukin-15 on NK cell anti-human immunodeficiency virus activity. J Virol 2004; 78:6033–6042.

    Article  PubMed  CAS  Google Scholar 

  30. Peng BG, Liang LJ, He Q, Huang JF, Lu MD. Expansion and activation of natural killer cells from PBMC for immunotherapy of hepatocellular carcinoma. World J Gastroenterol 2004; 10:2119–2123.

    PubMed  CAS  Google Scholar 

  31. Kennedy MK, Glaccum M, Brown SN, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 2000; 191:771–780.

    Article  PubMed  CAS  Google Scholar 

  32. Bigda J, Mysliwska J, Baran W, Hellmann A, Mysliwski A. Interleukin 2-and interferon alpha induced natural killer cell activity as a marker of progression in hairy cell leukemia. Leuk Lymphoma 1993; 9:371–376.

    PubMed  CAS  Google Scholar 

  33. Reiter Z, Ozes ON, Blatt LM, Taylor MW. Cytokine and natural killing regulation of growth of a hairy cell leukemia-like cell line: the role of interferon-alpha and interleukin-2. J Immunother 1992; 11:40–49.

    Article  PubMed  CAS  Google Scholar 

  34. Loza MJ, Perussia B. The IL-12 signature: NK cell terminal CD56+ high stage and effector functions. J Immunol 2004; 172:88–96.

    PubMed  CAS  Google Scholar 

  35. Robertson MJ, Cameron C, Atkins MB, et al. Immunological effects of interleukin 12 administered by bolus intravenous injection to patients with cancer. Clin Cancer Res 1999; 5:9–16.

    PubMed  CAS  Google Scholar 

  36. Liberati AM, De Angelis V, Fizzotti M, et al. Natural-killer-stimulatory effect of combined low-dose interleukin-2 and interferon beta in hairy-cell leukemia patients. Cancer Immunol Immunother 1994; 38:323–331.

    PubMed  CAS  Google Scholar 

  37. Atzpodien J, Kirchner H, Korfer A, et al. Expansion of peripheral blood natural killer cells correlates with clinical outcome in cancer patients receiving recombinant subcutaneous interleukin-2 and interferonalpha-2. Tumour Biol 1993; 14:354–359.

    Article  PubMed  CAS  Google Scholar 

  38. Zaki MH, Wysocka M, Everetts SE, et al. Synergistic enhancement of cell-mediated immunity by interleukin-12 plus interleukin-2: basis for therapy of cutaneous T cell lymphoma. J Invest Dermatol 2002; 118:366–371.

    Article  PubMed  CAS  Google Scholar 

  39. Ansell SM. Adding cytokines to monoclonal antibody therapy: does the concurrent administration of interleukin-12 add to the efficacy of rituximab in B-cell non-hodgkin lymphoma? Leuk Lymphoma 2003; 44:1309–1315.

    Article  PubMed  CAS  Google Scholar 

  40. Gluck WL, Hurst D, Yuen A, et al. Phase I studies of interleukin (IL)-2 and rituximab in B-cell non-Hodgkin’s lymphoma: IL-2 mediated natural killer cell expansion correlations with clinical response. Clin Cancer Res 2004; 10:2253–2264.

    Article  PubMed  CAS  Google Scholar 

  41. Repka T, Chiorean EG, Gay J, et al. Trastuzumab and interleukin-2 in HER2-positive metastatic breast cancer: a pilot study. Clin Cancer Res 2003; 9:2440–2446.

    PubMed  CAS  Google Scholar 

  42. Krause SW, Gastpar R, Andreesen R, et al. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase I trial. Clin Cancer Res 2004; 10:3699–3707.

    Article  PubMed  CAS  Google Scholar 

  43. Xu D, Gu P, Pan PY, Li Q, Sato AI, Chen SH. NK and CD8+ T cell-mediated eradication of poorly immunogenic B16-F10 melanoma by the combined action of IL-12 gene therapy and 4-1BB costimulation. Int J Cancer 2004; 109:499–506.

    Article  PubMed  CAS  Google Scholar 

  44. Robertson MJ. Role of chemokines in the biology of natural killer cells. J Leukoc Biol 2002; 71:173–183.

    PubMed  CAS  Google Scholar 

  45. Robinson LA, Nataraj C, Thomas DW, et al. The chemokine CX3CL1 regulates NK cell activity in vivo. Cell Immunol 2003; 225:122–130.

    Article  PubMed  CAS  Google Scholar 

  46. Guo J, Chen T, Wang B, et al. Chemoattraction, adhesion and activation of natural killer cells are involved in the antitumor immune response induced by fractalkine/CX3CL1. Immunol Lett 2003; 89:1–7.

    Article  PubMed  CAS  Google Scholar 

  47. Amakata Y, Fujiyama Y, Andoh A, Hodohara K, Bamba T. Mechanism of NK cell activation induced by coculture with dendritic cells derived from peripheral blood monocytes. Clin Exp Immunol 2001; 124:214–222.

    Article  PubMed  CAS  Google Scholar 

  48. Turner JG, Rakhmilevich AL, Burdelya L, et al. Anti-CD40 antibody induces antitumor and antimetastatic effects: the role of NK cells. J Immunol 2001; 166:89–94.

    PubMed  CAS  Google Scholar 

  49. Powzaniuk MA, Trotta R, Loza MJ, et al. B-Myb overexpression results in activation and increased Fas/ Fas ligand-mediated cytotoxicity of T and NK cells. J Immunol 2001; 167:242–249.

    PubMed  CAS  Google Scholar 

  50. Davies FE, Raje N, Hideshima T, et al. Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma. Blood 2001; 98:210–216.

    Article  PubMed  CAS  Google Scholar 

  51. Lozupone F, Pende D, Burgio VL, et al. Effect of human natural killer and gammadelta T cells on the growth of human autologous melanoma xenografts in SCID mice. Cancer Res 2004; 64:378–385.

    Article  PubMed  CAS  Google Scholar 

  52. Brand JM, Meller B, Von Hof K, et al. Kinetics and organ distribution of allogeneic natural killer lymphocytes transfused into patients suffering from renal cell carcinoma. Stem Cell Dev 2004; 13:307–314.

    Article  CAS  Google Scholar 

  53. Schirrmann T, Pecher G. Tumor-specific targeting of a cell line with natural killer cell activity by asialoglycoprotein receptor gene transfer. Cancer Immunol Immunother 2001; 50:549–556.

    Article  PubMed  CAS  Google Scholar 

  54. Schirrmann T, Pecher G. Human natural killer cell line modified with a chimeric immunoglobulin T-cell receptor gene leads to tumor growth inhibition in vivo. Cancer Gene Ther 2002; 9:390–398.

    Article  PubMed  CAS  Google Scholar 

  55. Yan Y, Steinherz P, Klingemann HG, et al. Antileukemia activity of a natural killer cell line against human leukemias. Clin Cancer Res 1998; 4:2859–2868.

    PubMed  CAS  Google Scholar 

  56. Zhang J, Sun R, Wei H, Tian Z. Characterization of interleukin-15 gene-modified human natural killer cells: implications for adoptive cellular immunotherapy. Haematologica 2004; 89:338–347.

    PubMed  CAS  Google Scholar 

  57. Zhang J, Sun R, Wei H, Tian Z. Characterization of stem cell factor gene-modified human natural killer cell line, NK-92 cells: implication in NK cell-based adoptive cellular immunotherapy. Oncol Rep 2004; 11:1097–1106.

    PubMed  CAS  Google Scholar 

  58. Hartmann F, Renner C, Jung W, et al. Anti-CD16/CD30 bispecific antibody treatment for Hodgkin’s disease: role of infusion schedule and costimulation with cytokines. Clin Cancer Res 2001; 7:1873–1881.

    PubMed  CAS  Google Scholar 

  59. Heuser C, Guhlke S, Matthies A, et al. Anti-CD30-scFv-Fc-IL-2 antibody-cytokine fusion protein that induces resting NK cells to highly efficient cytolysis of Hodgkin’s lymphoma derived tumour cells. Int J Cancer 2004; 110:386–394.

    Article  PubMed  CAS  Google Scholar 

  60. Hoffmann TK, Bier H, Whiteside TL. Targeting the immune system: novel therapeutic approaches in squamous cell carcinoma of the head and neck. Cancer Immunol Immunother 2004; 53:1055–1067.

    Article  PubMed  Google Scholar 

  61. Dudley ME, Rosenberg SA. Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer 2003; 3:666–675.

    Article  PubMed  CAS  Google Scholar 

  62. Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature 2001; 411:380–384.

    Article  PubMed  CAS  Google Scholar 

  63. Igarashi T, Wynberg J, Srinivasan R, et al. Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells. Blood 2004; 104:170–177.

    Article  PubMed  CAS  Google Scholar 

  64. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 2002; 295:2097–2100.

    Article  PubMed  CAS  Google Scholar 

  65. Velardi A, Ruggeri L, Moretta A, Moretta L. NK cells: a lesson from mismatched hematopoietic transplantation. Trends Immunol 2002; 23:438–444.

    Article  PubMed  CAS  Google Scholar 

  66. Leung W, Iyengar R, Turner V, et al. Determinants of antileukemia effects of allogeneic NK cells. J Immunol 2004; 172:644–650.

    PubMed  CAS  Google Scholar 

  67. Koh CY, Blazar BR, George T, et al. Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo. Blood 2001; 97:3132–3237.

    Article  PubMed  CAS  Google Scholar 

  68. Koh CY, Raziuddin A, Welniak LA, Blazar BR, Bennett M, Murphy WJ. NK inhibitory-receptor blockade for purging of leukemia: effects on hematopoietic reconstitution. Biol Blood Marrow Transplant 2002; 8:17–25.

    Article  PubMed  CAS  Google Scholar 

  69. Asai O, Longo DL, Tian ZG, et al. Suppression of graft-versus-host disease and amplification of graftversus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation. J Clin Invest 1998; 101:1835–1842.

    PubMed  CAS  Google Scholar 

  70. Rosenthal FM, Zier KS, Gansbacher B. Human tumor vaccines and genetic engineering of tumors with cytokine and histocompatibility genes to enhance immunogenicity. Curr Opin Oncol 1994; 6:611–615.

    Article  PubMed  CAS  Google Scholar 

  71. Rosenthal FM, Cronin K, Bannerji R, Golde DW, Gansbacher B. Augmentation of antitumor immunity by tumor cells transduced with a retroviral vector carrying the interleukin-2 and interferon-gamma cDNAs. Blood 1994; 83:1289–1298.

    PubMed  CAS  Google Scholar 

  72. Bannerji R, Arroyo CD, Cordon-Cardo C, Gilboa E. The role of IL-2 secreted from genetically modified tumor cells in the establishment of antitumor immunity. J Immunol 1994; 152:2324–2332.

    PubMed  CAS  Google Scholar 

  73. Yang S, Vervaert CE, Seigler HF, Darrow TL. Tumor cells cotransduced with B7.1 and gamma-IFN induce effective rejection of established parental tumor. Gene Ther 1999; 6:253–262.

    Article  PubMed  CAS  Google Scholar 

  74. Kundu N, Fulton AM. Interleukin-10 inhibits tumor metastasis, downregulates MHC class I, and enhances NK lysis. Cell Immunol 1997; 180:55–61.

    Article  PubMed  CAS  Google Scholar 

  75. Ugai S, Shimozato O, Yu L, et al. Transduction of the IL-21 and IL-23 genes in human pancreatic carcinoma cells produces natural killer cell-dependent and-independent antitumor effects. Cancer Gene Ther 2003; 10:771–778.

    Article  PubMed  CAS  Google Scholar 

  76. Braun SE, Chen K, Foster RG, et al. The CC chemokine CK beta-11/MIP-3 beta/ELC/Exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells. J Immunol 2000; 164:4025–4031.

    PubMed  CAS  Google Scholar 

  77. Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 2001; 413:165–171.

    Article  PubMed  CAS  Google Scholar 

  78. Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo. Proc Natl Acad Sci USA 2001; 98:11,521–11,526.

    Article  PubMed  CAS  Google Scholar 

  79. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 2002; 419:734–738.

    Article  PubMed  CAS  Google Scholar 

  80. Wu JD, Higgins LM, Steinle A, Cosman D, Haugk K, Plymate SR. Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J Clin Invest 2004; 114:560–568.

    Article  PubMed  CAS  Google Scholar 

  81. Salih HR, Rammensee HG, Steinle A. Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 2002; 169:4098–4102.

    PubMed  CAS  Google Scholar 

  82. de Visser KE, Kast WM. Effects of TGF-beta on the immune system: implications for cancer immunotherapy. Leukemia 1999; 13:1188–1199.

    Article  PubMed  Google Scholar 

  83. 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.

    PubMed  CAS  Google Scholar 

  84. Seo N, Tokura Y, Takigawa M, Egawa K. Depletion of IL-10-and TGF-beta-producing regulatory gamma delta T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells. J Immunol 1999; 163:242–249.

    PubMed  CAS  Google Scholar 

  85. 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.

    PubMed  CAS  Google Scholar 

  86. Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM, Forbes JT. 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.

    Article  PubMed  CAS  Google Scholar 

  87. Mailliard RB, Son YI, Redlinger R, et al. Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol 2003; 171:2366–2373.

    PubMed  CAS  Google Scholar 

  88. Moretta L, Ferlazzo G, Mingari MC, Melioli G, Moretta A. Human natural killer cell function and their interactions with dendritic cells. Vaccine 2003; 21(Suppl 2):S38–S42.

    Article  PubMed  CAS  Google Scholar 

  89. Alli RS, Khar A. Interleukin-12 secreted by mature dendritic cells mediates activation of NK cell function. FEBS Lett 2004; 559:71–76.

    Article  PubMed  CAS  Google Scholar 

  90. Westwood JA, Kelly JM, Tanner JE, Kershaw MH, Smyth MJ, Hayakawa Y. Cutting edge: novel priming of tumor-specific immunity by NKG2D-triggered NK cell-mediated tumor rejection and Th1-independent CD4+ T cell pathway. J Immunol 2004; 172:757–761.

    PubMed  CAS  Google Scholar 

  91. Akbar SM, Murakami H, Horiike N, Onji M. Dendritic cell-based therapies in the bench and the bedsides. Curr Drug Targets Inflamm Allergy 2004; 3:305–310.

    Article  PubMed  CAS  Google Scholar 

  92. Albertsson PA, Basse PH, Hokland M, et al. NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity. Trends Immunol 2003; 24:603–609.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

    Lisa M. Harlan PhD & Julie Y. Djeu PhD

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  1. Lisa M. Harlan PhD
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  2. Julie Y. Djeu PhD
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  1. University of Washington School of Medicine, Seattle, WA

    Mary L. Disis MD

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Harlan, L.M., Djeu, J.Y. (2006). Current and Future Role of Natural-Killer Cells in Cancer Immunotherapy. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:045

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