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Natural Killer Cells for Cancer Immunotherapy

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Abstract

Natural killer (NK) cells are immune effector cells that have long been known to possess potent cytotoxic ability. Despite this, NK cells remained relatively underrepresented in the medical literature, due in part to the strong emphasis placed on studying the mechanisms of the antigenic specificity and memory of T and B lymphocytes. Fortunately, as innate cells have gained prominence in recent years, NK cell research has blossomed and we now have a glimpse of the complexity of these cells and the potential that they have in cancer therapy. Not only do NK cells have a powerful ability to directly kill abnormal cells, they play a critical role in shaping adaptive responses by secreting a wide array of regulatory factors and interacting with multiple cell types. This chapter provides an overview of the current understanding of human NK cells, and discusses the potential of taking advantage of this knowledge to use NK cells in cancer therapy. Although much of our knowledge of NK cell biology comes from mouse studies, many of which involved models of viral or auto-immune diseases, the focus here is on observations made with human NK cells in the context of cancer.

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References

  1. Herberman RB, Nunn ME and Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer 16(2):216–229

    Article  PubMed  CAS  Google Scholar 

  2. Kiessling R, Klein E and Wigzell H (1975) “Natural” killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 5(2):112–117

    Article  PubMed  CAS  Google Scholar 

  3. Kumar V, George T, Yu YY et al (1997) Role of murine NK cells and their receptors in hybrid resistance. Curr Opin Immunol 9(1):52–56

    Article  PubMed  CAS  Google Scholar 

  4. Caligiuri MA (2008) Human natural killer cells. Blood 112(3):461–9

    Article  PubMed  CAS  Google Scholar 

  5. Long EO (2007) Ready for prime time: NK cell priming by dendritic cells. Immunity 26(4):385–387

    Article  PubMed  CAS  Google Scholar 

  6. Sun JC, Beilke JN and Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457(7229):557–561

    Article  PubMed  CAS  Google Scholar 

  7. Cella M, Fuchs A, Vermi W et al (2009) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457(7230):722–725

    Article  PubMed  CAS  Google Scholar 

  8. Santoni A, Zingoni A, Cerboni C et al (2007) Natural killer (NK) cells from killers to regulators: distinct features between peripheral blood and decidual NK cells. Am J Reprod Immunol 58(3):280–288

    Article  PubMed  CAS  Google Scholar 

  9. Vosshenrich CA, Garcia-Ojeda ME, Samson-Villeger SI et al (2006) A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127. Nat Immunol 7(11):1217–1224

    Article  PubMed  CAS  Google Scholar 

  10. Poli A, Michel T, Theresine M et al (2009) CD56bright natural killer (NK) cells: an important NK cell subset. Immunology 126(4):458–465

    Article  PubMed  CAS  Google Scholar 

  11. Fehniger TA, Cooper MA, Nuovo GJ et al (2003) CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood 101(8):3052–3057

    Article  PubMed  CAS  Google Scholar 

  12. Carson W and Caligiuri M (1996) Natural killer cell subsets and development. Methods 9(2):327–343

    Article  PubMed  CAS  Google Scholar 

  13. Chan A, Hong DL, Atzberger A et al (2007) CD56bright human NK cells differentiate into CD56dim cells: role of contact with peripheral fibroblasts. J Immunol 179(1):89–94

    PubMed  CAS  Google Scholar 

  14. Hayakawa Y and Smyth MJ (2006) CD27 dissects mature NK cells into two subsets with distinct responsiveness and migratory capacity. J Immunol 176(3):1517–15 24

    PubMed  CAS  Google Scholar 

  15. Cullen SP and Martin SJ (2008) Mechanisms of granule-dependent killing. Cell Death Differ 15(2):251–262

    Article  PubMed  CAS  Google Scholar 

  16. Ashkenazi A, Holland P and Eckhardt SG (2008) Ligand-based targeting of apoptosis in cancer: the potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). J Clin Oncol 26(21):3621–3630

    Article  PubMed  CAS  Google Scholar 

  17. Schoenborn JR and Wilson CB (2007) Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 96:41–101

    Article  PubMed  CAS  Google Scholar 

  18. Robertson MJ (2002) Role of chemokines in the biology of natural killer cells. J Leukoc Biol 71(2):173–183

    PubMed  CAS  Google Scholar 

  19. Coughlin CM, Salhany KE, Gee MS et al (1998) Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis. Immunity 9(1):25–34

    Article  PubMed  CAS  Google Scholar 

  20. Sidky YA and Borden EC (1987) Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. Cancer Res 47(19):5155–5161

    PubMed  CAS  Google Scholar 

  21. Karre K, Ljunggren HG, Piontek G et al (1986) Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319(6055):675–678

    Article  PubMed  CAS  Google Scholar 

  22. Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274

    Article  PubMed  CAS  Google Scholar 

  23. Norman PJ and Parham P (2005) Complex interactions: the immunogenetics of human leukocyte antigen and killer cell immunoglobulin-like receptors. Semin Hematol 42(2):65–75

    Article  PubMed  CAS  Google Scholar 

  24. Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5(3):201–214

    Article  PubMed  CAS  Google Scholar 

  25. Cooley S, Trachtenberg E, Bergemann TL et al (2009) Donors with group B KIR haplotypes improve relapse-free survival after unrelated hematopoietic cell transplantation for acute myelogenous leukemia. Blood 113(3):726–732

    Article  PubMed  CAS  Google Scholar 

  26. Braud VM, Allan DS, O’Callaghan CA et al (1998) HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391(6669):795–799

    Article  PubMed  CAS  Google Scholar 

  27. Nguyen S, Dhedin N, Vernant JP et al (2005) NK-cell reconstitution after haploidentical hematopoietic stem-cell transplantations: immaturity of NK cells and inhibitory effect of NKG2A override GvL effect. Blood 105(10):4135–4142

    Article  PubMed  CAS  Google Scholar 

  28. Guerra N, Tan YX, Joncker NT et al (2008) NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28(4):571–580

    Article  PubMed  CAS  Google Scholar 

  29. Smyth MJ, Swann J, Cretney E et al (2005) NKG2D function protects the host from tumor initiation. J Exp Med 202(5):583–588

    Article  PubMed  CAS  Google Scholar 

  30. Moretta L, Bottino C, Pende D et al (2006) Surface NK receptors and their ligands on tumor cells. Semin Immunol 18(3):151–158

    Article  PubMed  CAS  Google Scholar 

  31. Doubrovina ES, Doubrovin MM, Vider E et al (2003) Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J Immunol 171(12):6891–6899

    PubMed  CAS  Google Scholar 

  32. Arnon TI, Markel G and Mandelboim O (2006) Tumor and viral recognition by natural killer cells receptors. Semin Cancer Biol 16(5):348–358

    Article  PubMed  CAS  Google Scholar 

  33. Fauriat C, Just-Landi S, Mallet F et al (2007) Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction. Blood 109(1):323–330

    Article  PubMed  CAS  Google Scholar 

  34. Pogge von Strandmann E, Simhadri VR, von Tresckow B et al (2007) Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 27(6):965–974

    Article  PubMed  CAS  Google Scholar 

  35. Arnon TI, Markel G, Bar-Ilan A et al (2008) Harnessing soluble NK cell killer receptors for the generation of novel cancer immune therapy. PLoS ONE 3(5):e2150

    Article  PubMed  CAS  Google Scholar 

  36. Pende D, Spaggiari GM, Marcenaro S et al (2005) Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112). Blood 105(5):2066–2073

    Article  PubMed  CAS  Google Scholar 

  37. El-Sherbiny YM, Meade JL, Holmes TD et al (2007) The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Res 67(18):8444–8449

    Article  PubMed  CAS  Google Scholar 

  38. Nedvetzki S, Sowinski S, Eagle RA et al (2007) Reciprocal regulation of human natural killer cells and macrophages associated with distinct immune synapses. Blood 109(9):3776–3785

    Article  PubMed  CAS  Google Scholar 

  39. Bryceson YT, March ME, Ljunggren HG et al (2006) Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 107(1):159–166

    Article  PubMed  CAS  Google Scholar 

  40. Bryceson YT, March ME, Ljunggren HG et al (2006) Activation, coactivation, and costimulation of resting human natural killer cells. Immunol Rev 214:73–91

    Article  PubMed  CAS  Google Scholar 

  41. Miller JS, Tessmer-Tuck J, Pierson BA et al (1997) Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity. Biol Blood Marrow Transplant 3(1):34–44

    PubMed  CAS  Google Scholar 

  42. Lucas M, Schachterle W, Oberle K et al (2007) Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity 26(4):503–517

    Article  PubMed  CAS  Google Scholar 

  43. Skak K, Kragh M, Hausman D et al (2008) Interleukin 21: combination strategies for cancer therapy. Nat Rev Drug Discov 7(3):231–240

    Article  PubMed  CAS  Google Scholar 

  44. Ghiringhelli F, Menard C, Martin F et al (2006) The role of regulatory T cells in the control of natural killer cells: relevance during tumor progression. Immunol Rev 214:229–238

    Article  PubMed  CAS  Google Scholar 

  45. Clayton A, Mitchell JP, Court J et al (2008) Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 180(11):7249–7258

    PubMed  CAS  Google Scholar 

  46. Spaggiari GM, Capobianco A, Abdelrazik H et al (2008) Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood 111(3):1327–1333

    Article  PubMed  CAS  Google Scholar 

  47. Street SE, Hayakawa Y, Zhan Y et al (2004) Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med 199(6):879–884

    Article  PubMed  CAS  Google Scholar 

  48. Imai K, Matsuyama S, Miyake S et al (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356(9244):1795–1799

    Article  PubMed  CAS  Google Scholar 

  49. Re F, Staudacher C, Zamai L et al (2006) Killer cell Ig-like receptors ligand-mismatched, alloreactive natural killer cells lyse primary solid tumors. Cancer 107(3):640–648

    Article  PubMed  CAS  Google Scholar 

  50. Coca S, Perez-Piqueras J, Martinez D et al (1997) The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79(12):2320–2328

    Article  PubMed  CAS  Google Scholar 

  51. Hsia JY, Chen JT, Chen CY et al (2005) Prognostic significance of intratumoral natural killer cells in primary resected esophageal squamous cell carcinoma. Chang Gung Med J 28(5):335–340

    PubMed  Google Scholar 

  52. Ishigami S, Natsugoe S, Tokuda K et al (2000) Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 88(3):577–583

    Article  PubMed  CAS  Google Scholar 

  53. Villegas FR, Coca S, Villarrubia VG et al (2002) Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 35(1):23–28

    Article  PubMed  Google Scholar 

  54. Zhu LY, Zhou J, Liu YZ et al (2009) Prognostic significance of natural killer cell infiltration in hepatocellular carcinoma. Chin J Cancer 28(11):1198–1202

    Article  Google Scholar 

  55. Carrega P, Morandi B, Costa R et al (2008) Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(-) cells and display an impaired capability to kill tumor cells. Cancer 112(4):863–875

    Article  PubMed  Google Scholar 

  56. Schleypen JS, Baur N, Kammerer R et al (2006) Cytotoxic markers and frequency predict functional capacity of natural killer cells infiltrating renal cell carcinoma. Clin Cancer Res 12(3 Pt 1):718–725

    Article  PubMed  CAS  Google Scholar 

  57. Dudley ME and Rosenberg SA (2003) Adoptive-cell-transfer therapy for the treatment of patients with cancer. Nat Rev Cancer 3(9):666–675

    Article  PubMed  CAS  Google Scholar 

  58. Ahmadzadeh M and Rosenberg SA (2006) IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 107(6):2409–2414

    Article  PubMed  CAS  Google Scholar 

  59. Zhang H, Chua KS, Guimond M et al (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+ CD25+ regulatory T cells. Nat Med 11(11):1238–1243

    Article  PubMed  CAS  Google Scholar 

  60. Bates GJ, Fox SB, Han C et al (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24(34):5373–5380

    Article  PubMed  Google Scholar 

  61. Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949

    Article  PubMed  CAS  Google Scholar 

  62. Kono K, Kawaida H, Takahashi A et al (2006) CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother 55(9):1064–1071

    Article  PubMed  CAS  Google Scholar 

  63. Ruggeri L, Capanni M, Urbani E et al (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295(5562):2097–2100

    Article  PubMed  CAS  Google Scholar 

  64. Miller JS, Soignier Y, Panoskaltsis-Mortari A et al (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105(8):3051–3057

    Article  PubMed  CAS  Google Scholar 

  65. Gill S, Olson JA and Negrin RS (2009) Natural killer cells in allogeneic transplantation: effect on engraftment, graft-versus-tumor, and graft-versus-host responses. Biol Blood Marrow Transplant 15(7):765–776

    Article  PubMed  CAS  Google Scholar 

  66. Berg M, Lundqvist A, McCoy P, Jr. et al (2009) Clinical-grade ex vivo-expanded human natural killer cells up-regulate activating receptors and death receptor ligands and have enhanced cytolytic activity against tumor cells. Cytotherapy 23:1–15

    Google Scholar 

  67. Luhm J, Brand JM, Koritke P et al (2002) Large-scale generation of natural killer lymphocytes for clinical application. J Hematother Stem Cell Res 11(4):651–657

    Article  PubMed  Google Scholar 

  68. McKenna DH, Jr., Sumstad D, Bostrom N et al (2007) Good manufacturing practices production of natural killer cells for immunotherapy: a six-year single-institution experience. Transfusion 47(3):520–528

    Article  PubMed  CAS  Google Scholar 

  69. Albertsson PA, Basse PH, Hokland M et al (2003) NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity. Trends Immunol 24(11):603–609

    Article  PubMed  CAS  Google Scholar 

  70. Gao JQ, Okada N, Mayumi T et al (2008) Immune cell recruitment and cell-based system for cancer therapy. Pharm Res 25(4):752–768

    Article  PubMed  CAS  Google Scholar 

  71. Matera L, Galetto A, Bello M et al (2006) In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma. J Transl Med 4:49

    Google Scholar 

  72. Klingemann HG, Wong E and Maki G (1996) A cytotoxic NK-cell line (NK-92) for ex vivo purging of leukemia from blood. Biol Blood Marrow Transplant 2(2):68–75

    PubMed  CAS  Google Scholar 

  73. Suck G, Branch DR and Keating A (2006) Irradiated KHYG-1 retains cytotoxicity: potential for adoptive immunotherapy with a natural killer cell line. Int J Radiat Biol 82(5):355–361

    Article  PubMed  CAS  Google Scholar 

  74. Tam YK, Martinson JA, Doligosa K et al (2003) Ex vivo expansion of the highly cytotoxic human natural killer-92 cell-line under current good manufacturing practice conditions for clinical adoptive cellular immunotherapy. Cytotherapy 5(3):259–272

    Article  PubMed  CAS  Google Scholar 

  75. Yan Y, Steinherz P, Klingemann HG et al (1998) Antileukemia activity of a natural killer cell line against human leukemias. Clin Cancer Res 4(11):2859–2868

    PubMed  CAS  Google Scholar 

  76. Tam YK, Miyagawa B, Ho VC et al (1999) Immunotherapy of malignant melanoma in a SCID mouse model using the highly cytotoxic natural killer cell line NK-92. J Hematother 8(3):281–290

    Article  PubMed  CAS  Google Scholar 

  77. Tonn T, Becker S, Esser R et al (2001) Cellular immunotherapy of malignancies using the clonal natural killer cell line NK-92. J Hematother Stem Cell Res 10(4):535–544

    Article  PubMed  CAS  Google Scholar 

  78. Arai S, Meagher R, Swearingen M et al (2008) Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial. Cytotherapy 10(6):625–632

    Article  PubMed  CAS  Google Scholar 

  79. Nagashima S, Mailliard R, Kashii Y et al (1998) Stable transduction of the interleukin-2 gene into human natural killer cell lines and their phenotypic and functional characterization in vitro and in vivo. Blood 91(10):3850–3861

    PubMed  CAS  Google Scholar 

  80. Zhang J, Sun R, Wei H et al (2004) Characterization of interleukin-15 gene-modified human natural killer cells: implications for adoptive cellular immunotherapy. Haematologica 89(3):338–347

    PubMed  CAS  Google Scholar 

  81. Demirtzoglou FJ, Papadopoulos S and Zografos G (2006) Cytolytic and cytotoxic activity of a human natural killer cell line genetically modified to specifically recognize HER-2/neu overexpressing tumor cells. Immunopharmacol Immunotoxicol 28(4):571–590

    Article  PubMed  CAS  Google Scholar 

  82. Boissel L, Betancur M, Wels WS et al (2009) Transfection with mRNA for CD19 specific chimeric antigen receptor restores NK cell mediated killing of CLL cells. Leuk Res 33(9):1255–1259

    Article  PubMed  CAS  Google Scholar 

  83. Muller T, Uherek C, Maki G et al (2008) Expression of a CD20-specific chimeric antigen receptor enhances cytotoxic activity of NK cells and overcomes NK-resistance of lymphoma and leukemia cells. Cancer Immunol Immunother 57(3):411–423

    Article  PubMed  CAS  Google Scholar 

  84. Suck G, Branch DR, Aravena P et al (2006) Constitutively polarized granules prime KHYG-1 NK cells. Int Immunol 18(9):1347–1354

    Article  PubMed  CAS  Google Scholar 

  85. Suck G, Branch DR, Smyth MJ et al (2005) KHYG-1, a model for the study of enhanced natural killer cell cytotoxicity. Exp Hematol 33(10):1160–1171

    Article  PubMed  CAS  Google Scholar 

  86. Clynes RA, Towers TL, Presta LG et al (2000) Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nat Med 6(4):443–446

    Article  PubMed  CAS  Google Scholar 

  87. Cartron G, Dacheux L, Salles G et al (2002) Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcgammaRIIIa gene. Blood 99(3):754–758

    Article  PubMed  CAS  Google Scholar 

  88. Friedberg JW, Neuberg D, Gribben JG et al (2002) Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin’s lymphoma. Br J Haematol 117(4):828–834

    Article  PubMed  CAS  Google Scholar 

  89. Gluck WL, Hurst D, Yuen A et al (2004) 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 10(7):2253–2264

    Article  PubMed  CAS  Google Scholar 

  90. Khan KD, Emmanouilides C, Benson DM, Jr. et al (2006) A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non- Hodgkin’s lymphoma. Clin Cancer Res 12(23):7046–7053

    Article  PubMed  CAS  Google Scholar 

  91. Berdeja JG, Hess A, Lucas DM et al (2007) Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-cell lymphoma treated with rituximab. Clin Cancer Res 13(8):2392–2399

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  93. Ansell SM, Geyer SM, Maurer MJ et al (2006) Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin’s lymphoma patients. Clin Cancer Res 12(20 Pt 1):6056–6063

    Article  PubMed  CAS  Google Scholar 

  94. Bekaii-Saab TS, Roda JM, Guenterberg KD et al (2009) A phase I trial of paclitaxel and trastuzumab in combination with interleukin-12 in patients with HER2/neu-expressing malignancies. Mol Cancer Ther 8(11):2983–2991

    Article  PubMed  CAS  Google Scholar 

  95. Parihar R, Nadella P, Lewis A et al (2004) A phase I study of interleukin 12 with trastuzumab in patients with human epidermal growth factor receptor-2-overexpressing malignancies: analysis of sustained interferon gamma production in a subset of patients. Clin Cancer Res 10(15):5027–5037

    Article  PubMed  CAS  Google Scholar 

  96. Roda JM, Parihar R, Magro C et al (2006) Natural killer cells produce T cell-recruiting chemokines in response to antibody-coated tumor cells. Cancer Res 66(1):517–526

    Article  PubMed  CAS  Google Scholar 

  97. Kobayashi H, Dubois S, Sato N et al (2005) Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105(2):721–727

    Article  PubMed  CAS  Google Scholar 

  98. Zhang M, Yao Z, Dubois S et al (2009) Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer. Proc Natl Acad Sci USA 106(18):7513–7518

    Article  PubMed  CAS  Google Scholar 

  99. Roda JM, Joshi T, Butchar JP et al (2007) The activation of natural killer cell effector functions by cetuximab-coated, epidermal growth factor receptor positive tumor cells is enhanced by cytokines. Clin Cancer Res 13(21):6419–6428

    Article  PubMed  CAS  Google Scholar 

  100. Roda JM, Parihar R, Lehman A et al (2006) Interleukin-21 enhances NK cell activation in response to antibody-coated targets. J Immunol 177(1):120–129

    PubMed  CAS  Google Scholar 

  101. Daniel D, Yang B, Lawrence DA et al (2007) Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts. Blood 110(12):4037–4046

    Article  PubMed  CAS  Google Scholar 

  102. Wolska A, Lech-Maranda E and Robak T (2009) Toll-like receptors and their role in carcinogenesis and anti-tumor treatment. Cell Mol Biol Lett 14(2):248–272

    Article  PubMed  CAS  Google Scholar 

  103. Roda JM, Parihar R and Carson WE, 3rd (2005) CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol 175(3):1619–1627

    PubMed  CAS  Google Scholar 

  104. Link BK, Ballas ZK, Weisdorf D et al (2006) Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma. J Immunother 29(5):558–568

    Article  PubMed  CAS  Google Scholar 

  105. Chen W, Chan AS, Dawson AJ et al (2005) FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides to enhance T-cell and natural killer cell function. Biol Blood Marrow Transplant 11(1):23–34

    Article  PubMed  CAS  Google Scholar 

  106. Reddy N, Hernandez-Ilizaliturri FJ, Deeb G et al (2008) Immunomodulatory drugs stimulate natural killer-cell function, alter cytokine production by dendritic cells, and inhibit angiogenesis enhancing the anti-tumour activity of rituximab in vivo. Br J Haematol 140(1):36–45

    PubMed  CAS  Google Scholar 

  107. Wu L, Adams M, Carter T et al (2008) lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res 14(14):4650–4657

    Article  PubMed  CAS  Google Scholar 

  108. Borg C, Terme M, Taieb J et al (2004) Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest 114(3):379–388

    PubMed  CAS  Google Scholar 

  109. Koh CY, Blazar BR, George T et al (2001) Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo. Blood 97(10):3132–3137

    Article  PubMed  CAS  Google Scholar 

  110. Sheridan C (2006) First-in-class cancer therapeutic to stimulate natural killer cells. Nat Biotechnol 24(6):597

    Article  PubMed  CAS  Google Scholar 

  111. Jinushi M, Hodi FS and Dranoff G (2006) Therapy-induced antibodies to MHC class I chain-related protein A antagonize immune suppression and stimulate antitumor cytotoxicity. Proc Natl Acad Sci USA 103(24):9190–9195

    Article  PubMed  CAS  Google Scholar 

  112. Mao CP, Hung CF and Wu TC (2007) Immunotherapeutic strategies employing RNA interference technology for the control of cancers. J Biomed Sci 14(1):15–29

    Article  PubMed  CAS  Google Scholar 

  113. Lundqvist A, Abrams SI, Schrump DS et al (2006) Bortezomib and depsipeptide sensitize tumors to tumor necrosis factor-related apoptosis-inducing ligand: a novel method to potentiate natural killer cell tumor cytotoxicity. Cancer Res 66(14):7317–7325

    Article  PubMed  CAS  Google Scholar 

  114. Shi J, Tricot GJ, Garg TK et al (2008) Bortezomib down-regulates the cell-surface expression of HLA class I and enhances natural killer cell-mediated lysis of myeloma. Blood 111(3):1309–1317

    Article  PubMed  CAS  Google Scholar 

  115. Armeanu S, Bitzer M, Lauer UM et al (2005) Natural killer cell-mediated lysis of hepatoma cells via specific induction of NKG2D ligands by the histone deacetylase inhibitor sodium valproate. Cancer Res 65(14):6321–6329

    Article  PubMed  CAS  Google Scholar 

  116. Schmudde M, Braun A, Pende D et al (2008) Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells. Cancer Lett 272(1):110–121

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, University of Toronto, ON, Toronto, Canada

    Armand Keating

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  1. Yoko Kosaka
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  2. Armand Keating
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Correspondence to Armand Keating .

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  1. University Health Network, University of Toronto, College Street 67, Toronto, M5G 2M1, Ontario, Canada

    Jeffrey Medin

  2. National Cancer Institute, Experimental Transplatation &, National Institutes of Health, Center Drive 10, Bethesda, 20892, Maryland, USA

    Daniel Fowler

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© 2011 Springer Science+Business Media, LLC

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Kosaka, Y., Keating, A. (2011). Natural Killer Cells for Cancer Immunotherapy. In: Medin, J., Fowler, D. (eds) Experimental and Applied Immunotherapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-980-2_4

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