1932

Abstract

Natural killer (NK) cells have evolved to complement T and B cells in host defense against pathogens and cancer. They recognize infected cells and tumors using a sophisticated array of activating, costimulatory, and inhibitory receptors that are expressed on NK cell subsets to create extensive functional diversity. NK cells can be targeted to kill with exquisite antigen specificity by antibody-dependent cellular cytotoxicity. NK and T cells share many of the costimulatory and inhibitory receptors that are currently under evaluation in the clinic for cancer immunotherapy. As with T cells, genetic engineering is being employed to modify NK cells to specifically target them to tumors and to enhance their effector functions. As the selective pressures exerted by immunotherapies to augment CD8+ T cell responses may result in loss of MHC class I, NK cells may provide an important fail-safe to eliminate these tumors by their capacity to eliminate tumors that are “missing self.”

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-030518-055653
2019-03-04
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/3/1/annurev-cancerbio-030518-055653.html?itemId=/content/journals/10.1146/annurev-cancerbio-030518-055653&mimeType=html&fmt=ahah

Literature Cited

  1. Arai S, Meagher R, Swearingen M, Myint H, Rich E 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 10:625–32
    [Google Scholar]
  2. Arndt MA, Krauss J, Kipriyanov SM, Pfreundschuh M, Little M 1999. A bispecific diabody that mediates natural killer cell cytotoxicity against xenotransplantated human Hodgkin's tumors. Blood 94:2562–68
    [Google Scholar]
  3. Bachanova V, Burns LJ, McKenna DH, Curtsinger J, Panoskaltsis-Mortari A et al. 2010. Allogeneic natural killer cells for refractory lymphoma. Cancer Immunol. Immunother. 59:1739–44
    [Google Scholar]
  4. Bachanova V, Cooley S, Defor TE, Verneris MR, Zhang B et al. 2014. Clearance of acute myeloid leukemia by haploidentical natural killer cells is improved using IL-2 diphtheria toxin fusion protein. Blood 123:3855–63
    [Google Scholar]
  5. Baixeras E, Huard B, Miossec C, Jitsukawa S, Martin M et al. 1992. Characterization of the lymphocyte activation gene 3-encoded protein. A new ligand for human leukocyte antigen class II antigens. J. Exp. Med. 176:327–37
    [Google Scholar]
  6. Beldi-Ferchiou A, Lambert M, Dogniaux S, Vely F, Vivier E et al. 2016. PD-1 mediates functional exhaustion of activated NK cells in patients with Kaposi sarcoma. Oncotarget 7:72961–77
    [Google Scholar]
  7. Benson DM Jr., Bakan CE, Mishra A, Hofmeister CC, Efebera Y et al. 2010. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood 116:2286–94
    [Google Scholar]
  8. Benson DM Jr., Bakan CE, Zhang S, Collins SM, Liang J et al. 2011. IPH2101, a novel anti-inhibitory KIR antibody, and lenalidomide combine to enhance the natural killer cell versus multiple myeloma effect. Blood 118:6387–91
    [Google Scholar]
  9. Benson DM Jr., Cohen AD, Jagannath S, Munshi NC, Spitzer G et al. 2015. A phase I trial of the anti-KIR antibody IPH2101 and lenalidomide in patients with relapsed/refractory multiple myeloma. Clin. Cancer Res. 21:4055–61
    [Google Scholar]
  10. Benson DM Jr., Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S et al. 2012. A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood 120:4324–33
    [Google Scholar]
  11. Bergamaschi C, Watson DC, Valentin A, Bear J, Peer CJ et al. 2018. Optimized administration of hetIL-15 expands lymphocytes and minimizes toxicity in rhesus macaques. Cytokine 108:213–24
    [Google Scholar]
  12. Bertone S, Schiavetti F, Bellomo R, Vitale C, Ponte M et al. 1999. Transforming growth factor-beta-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes. Eur. J. Immunol. 29:23–29
    [Google Scholar]
  13. Bottino C, Castriconi R, Pende D, Rivera P, Nanni M et al. 2003. Identification of PVR (CD155) and nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J. Exp. Med. 198:557–67
    [Google Scholar]
  14. Bournazos S, Wang TT, Dahan R, Maamary J, Ravetch JV 2017. Signaling by antibodies: recent progress. Annu. Rev. Immunol. 35:285–311
    [Google Scholar]
  15. Brandt CS, Baratin M, Yi EC, Kennedy J, Gao Z et al. 2009. The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J. Exp. Med. 206:1495–503
    [Google Scholar]
  16. Braud VM, Allan DS, O'Callaghan CA, Soderstrom K, D'Andrea A et al. 1998. HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C. Nature 391:795–99
    [Google Scholar]
  17. Bruenke J, Barbin K, Kunert S, Lang P, Pfeiffer M et al. 2005. Effective lysis of lymphoma cells with a stabilised bispecific single-chain Fv antibody against CD19 and FcγRIII (CD16). Br. J. Haematol. 130:218–28
    [Google Scholar]
  18. Bruenke J, Fischer B, Barbin K, Schreiter K, Wachter Y et al. 2004. A recombinant bispecific single-chain Fv antibody against HLA class II and FcγRIII (CD16) triggers effective lysis of lymphoma cells. Br. J. Haematol. 125:167–79
    [Google Scholar]
  19. Bryceson YT, March ME, Ljunggren HG, Long EO 2006.a Activation, coactivation, and costimulation of resting human natural killer cells. Immunol. Rev. 214:73–91
    [Google Scholar]
  20. Bryceson YT, March ME, Ljunggren HG, Long EO 2006.b Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. Blood 107:159–66
    [Google Scholar]
  21. Burns LJ, Weisdorf DJ, DeFor TE, Vesole DH, Repka TL et al. 2003. IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I/II trial. Bone Marrow Transplant 32:177–86
    [Google Scholar]
  22. Carlsten M, Korde N, Kotecha R, Reger R, Bor S et al. 2016. Checkpoint inhibition of KIR2D with the monoclonal antibody IPH2101 induces contraction and hyporesponsiveness of NK cells in patients with myeloma. Clin. Cancer Res. 22:5211–22
    [Google Scholar]
  23. Chan SH, Perussia B, Gupta JW, Kobayashi M, Pospisil M et al. 1991. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J. Exp. Med. 173:869–79
    [Google Scholar]
  24. Charych DH, Hoch U, Langowski JL, Lee SR, Addepalli MK et al. 2016. NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumor exposure, and marked efficacy in mouse tumor models. Clin. Cancer Res. 22:680–90
    [Google Scholar]
  25. Cheng M, Chen Y, Xiao W, Sun R, Tian Z 2013. NK cell-based immunotherapy for malignant diseases. Cell Mol. Immunol. 10:230–52
    [Google Scholar]
  26. Chester C, Sanmamed MF, Wang J, Melero I 2018. Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies. Blood 131:49–57
    [Google Scholar]
  27. Cichocki F, Valamehr B, Bjordahl R, Zhang B, Rezner B et al. 2017. GSK3 inhibition drives maturation of NK cells and enhances their antitumor activity. Cancer Res 77:5664–75
    [Google Scholar]
  28. Ciurea SO, Schafer JR, Bassett R, Denman CJ, Cao K et al. 2017. Phase 1 clinical trial using mbIL21 ex vivo-expanded donor-derived NK cells after haploidentical transplantation. Blood 130:1857–68
    [Google Scholar]
  29. Colonna M, Navarro F, Bellon T, Llano M, Garcia P et al. 1997. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J. Exp. Med. 186:1809–18
    [Google Scholar]
  30. Colonna M, Samaridis J 1995. Cloning of Ig-superfamily members associated with HLA-C and HLA-B recognition by human NK cells. Science 268:405–8
    [Google Scholar]
  31. Conlon KC, Lugli E, Welles HC, Rosenberg SA, Fojo AT et al. 2015. Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer. J. Clin. Oncol. 33:74–82
    [Google Scholar]
  32. Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM 2009. Cytokine-induced memory-like natural killer cells. PNAS 106:1915–19
    [Google Scholar]
  33. Corral L, Hanke T, Vance RE, Cado D, Raulet DH 2000. NK cell expression of the killer cell lectin-like receptor G1 (KLRG1), the mouse homolog of MAFA, is modulated by MHC class I molecules. Eur. J. Immunol. 30:920–30
    [Google Scholar]
  34. Cortez VS, Ulland TK, Cervantes-Barragan L, Bando JK, Robinette ML et al. 2017. SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling. Nat. Immunol. 18:995–1003
    [Google Scholar]
  35. Cosman D, Fanger N, Borges L, Kibin M, Chin W et al. 1997. A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity 7:273–82
    [Google Scholar]
  36. D'Andrea A, Chang C, Franz-Bacon K, McClanahan T, Phillips JH, Lanier LL 1995. Cutting edge: molecular cloning of NKB1: a natural killer cell receptor for HLA-B allotypes. J. Immunol. 155:2306–10
    [Google Scholar]
  37. da Costa L, Renner C, Hartmann F, Pfreundschuh M 2000. Immune recruitment by bispecific antibodies for the treatment of Hodgkin disease. Cancer Chemother. Pharmacol. 46:Suppl.S33–36
    [Google Scholar]
  38. Dadi S, Chhangawala S, Whitlock BM, Franklin RA, Luo CT et al. 2016. Cancer immunosurveillance by tissue-resident innate lymphoid cells and innate-like T cells. Cell 164:365–77
    [Google Scholar]
  39. Das M, Zhu C, Kuchroo VK 2017. Tim-3 and its role in regulating anti-tumor immunity. Immunol. Rev. 276:97–111
    [Google Scholar]
  40. Denman CJ, Senyukov VV, Somanchi SS, Phatarpekar PV, Kopp LM et al. 2012. Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PLOS ONE 7:e30264
    [Google Scholar]
  41. Diefenbach A, Tomasello E, Lucas M, Jamieson AM, Hsia JK et al. 2002. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat. Immunol. 3:1142–49
    [Google Scholar]
  42. Dolstra H, Roeven MWH, Spanholtz J, Hangalapura BN, Tordoir M et al. 2017. Successful transfer of umbilical cord blood CD34+ hematopoietic stem and progenitor-derived NK cells in older acute myeloid leukemia patients. Clin. Cancer Res. 23:4107–18
    [Google Scholar]
  43. Dong Z, Cruz-Munoz ME, Zhong MC, Chen R, Latour S, Veillette A 2009. Essential function for SAP family adaptors in the surveillance of hematopoietic cells by natural killer cells. Nat. Immunol. 10:973–80
    [Google Scholar]
  44. Dougall WC, Kurtulus S, Smyth MJ, Anderson AC 2017. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol. Rev. 276:112–20
    [Google Scholar]
  45. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P et al. 2002. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298:850–54
    [Google Scholar]
  46. Elsasser D, Stadick H, Stark S, Van de Winkel JG, Gramatzki M et al. 1999. Preclinical studies combining bispecific antibodies with cytokine-stimulated effector cells for immunotherapy of renal cell carcinoma. Anticancer Res 19:1525–28
    [Google Scholar]
  47. Ettinghausen SE, Puri RK, Rosenberg SA 1988. Increased vascular permeability in organs mediated by the systemic administration of lymphokine-activated killer cells and recombinant interleukin-2 in mice. J. Natl. Cancer Inst. 80:177–88
    [Google Scholar]
  48. Felices M, Chu S, Kodal B, Bendzick L, Ryan C et al. 2017. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer. Gynecol. Oncol. 145:3453–61
    [Google Scholar]
  49. Ferrari de Andrade L, Tay RE, Pan R, Luoma AM, Ito Y et al. 2018. Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity. Science 359:1537–42
    [Google Scholar]
  50. Ferrini S, Cambiaggi A, Sforzini S, Canevari S, Mezzanzanica D et al. 1993. Use of anti-CD3 and anti-CD16 bispecific monoclonal antibodies for the targeting of T and NK cells against tumor cells. Cancer Detect. Prev. 17:295–300
    [Google Scholar]
  51. Ferrini S, Prigione I, Miotti S, Ciccone E, Cantoni C et al. 1991. Bispecific monoclonal antibodies directed to CD16 and to a tumor-associated antigen induce target-cell lysis by resting NK cells and by a subset of NK clones. Int. J. Cancer 48:227–33
    [Google Scholar]
  52. Fuchs A, Cella M, Giurisato E, Shaw AS, Colonna M 2004. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J. Immunol. 172:3994–98
    [Google Scholar]
  53. Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A et al. 2017. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat. Immunol. 18:1004–15
    [Google Scholar]
  54. Gasteiger G, Hemmers S, Firth MA, Le Floc'h A, Huse M et al. 2013. IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells. J. Exp. Med. 210:1167–78
    [Google Scholar]
  55. Geller MA, Cooley S, Judson PL, Ghebre R, Carson LF et al. 2011. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy 13:98–107
    [Google Scholar]
  56. Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J et al. 2005. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor–β–dependent manner. J. Exp. Med. 202:1075–85
    [Google Scholar]
  57. Gilfillan S, Chan CJ, Cella M, Haynes NM, Rapaport AS et al. 2008. DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors. J. Exp. Med. 205:2965–73
    [Google Scholar]
  58. Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M 2002. NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation. Nat. Immunol. 3:1150–55
    [Google Scholar]
  59. Gleason MK, Ross JA, Warlick ED, Lund TC, Verneris MR et al. 2014. CD16×CD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood 123:3016–26
    [Google Scholar]
  60. Gleason MK, Verneris MR, Todhunter DA, Zhang B, McCullar V et al. 2012. Bispecific and trispecific killer cell engagers directly activate human NK cells through CD16 signaling and induce cytotoxicity and cytokine production. Mol. Cancer Ther. 11:2674–84
    [Google Scholar]
  61. Glienke W, Esser R, Priesner C, Suerth JD, Schambach A et al. 2015. Advantages and applications of CAR-expressing natural killer cells. Front. Pharmacol. 6:21
    [Google Scholar]
  62. Glorius P, Baerenwaldt A, Kellner C, Staudinger M, Dechant M et al. 2013. The novel tribody [(CD20)2×CD16] efficiently triggers effector cell-mediated lysis of malignant B cells. Leukemia 27:190–201
    [Google Scholar]
  63. Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S et al. 1994. Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264:965–68
    [Google Scholar]
  64. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA 1982. 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. 155:1823–41
    [Google Scholar]
  65. Grundemann C, Bauer M, Schweier O, von Oppen N, Lassing U et al. 2006. Cutting edge: identification of E-cadherin as a ligand for the murine killer cell lectin-like receptor G1. J. Immunol. 176:1311–15
    [Google Scholar]
  66. Guillerey C, Ferrari de Andrade L, Vuckovic S, Miles K, Ngiow SF et al. 2015. Immunosurveillance and therapy of multiple myeloma are CD226 dependent. J. Clin. Investig. 125:2077–89
    [Google Scholar]
  67. Hartmann F, Renner C, Jung W, Deisting C, Juwana M et al. 1997. Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. Blood 89:2042–47
    [Google Scholar]
  68. Hartmann F, Renner C, Jung W, Pfreundschuh M 1998. Anti-CD16/CD30 bispecific antibodies as possible treatment for refractory Hodgkin's disease. Leuk. Lymphoma 31:385–92
    [Google Scholar]
  69. Herberman RB, Nunn ME, Lavrin DH 1975. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity. Int. J. Cancer 16:216–29
    [Google Scholar]
  70. Hermanson DL, Kaufman DS 2015. Utilizing chimeric antigen receptors to direct natural killer cell activity. Front. Immunol. 6:195
    [Google Scholar]
  71. Hoffman M, Mittelman A, Dworkin B, Rosenthal W, Beneck D et al. 1989. Severe intrahepatic cholestasis in patients treated with recombinant interleukin-2 and lymphokine-activated killer cells. J. Cancer Res. Clin. Oncol. 115:175–78
    [Google Scholar]
  72. Holliger P, Hudson PJ 2005. Engineered antibody fragments and the rise of single domains. Nat. Biotechnol. 23:1126–36
    [Google Scholar]
  73. Hombach A, Jung W, Pohl C, Renner C, Sahin U et al. 1993. A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo. Int. J. Cancer 55:830–36
    [Google Scholar]
  74. Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N et al. 2013. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci. Transl. Med. 5:208ra145
    [Google Scholar]
  75. Hosomi S, Chen Z, Baker K, Chen L, Huang YH et al. 2013. CEACAM1 on activated NK cells inhibits NKG2D-mediated cytolytic function and signaling. Eur. J. Immunol. 43:2473–83
    [Google Scholar]
  76. Huang BY, Zhan YP, Zong WJ, Yu CJ, Li JF et al. 2015.a The PD-1/B7-H1 pathway modulates the natural killer cells versus mouse glioma stem cells. PLOS ONE 10:e0134715
    [Google Scholar]
  77. Huang YH, Zhu C, Kondo Y, Anderson AC, Gandhi A et al. 2015.b CEACAM1 regulates TIM-3-mediated tolerance and exhaustion. Nature 517:386–90
    [Google Scholar]
  78. Huntington ND, Tabarias H, Fairfax K, Brady J, Hayakawa Y et al. 2007. NK cell maturation and peripheral homeostasis is associated with KLRG1 up-regulation. J. Immunol. 178:4764–70
    [Google Scholar]
  79. Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S et al. 2008. Accelerated tumor growth in mice deficient in DNAM-1 receptor. J. Exp. Med. 205:2959–64
    [Google Scholar]
  80. Imai C, Iwamoto S, Campana D 2005. Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood 106:376–83
    [Google Scholar]
  81. Iraolagoitia XL, Spallanzani RG, Torres NI, Araya RE, Ziblat A et al. 2016. NK cells restrain spontaneous antitumor CD8+ T cell priming through PD-1/PD-L1 interactions with dendritic cells. J. Immunol. 197:953–61
    [Google Scholar]
  82. Ito M, Maruyama T, Saito N, Koganei S, Yamamoto K, Matsumoto N 2006. Killer cell lectin-like receptor G1 binds three members of the classical cadherin family to inhibit NK cell cytotoxicity. J. Exp. Med. 203:289–95
    [Google Scholar]
  83. Johnson S, Burke S, Huang L, Gorlatov S, Li H et al. 2010. Effector cell recruitment with novel Fv-based dual-affinity re-targeting protein leads to potent tumor cytolysis and in vivo B-cell depletion. J. Mol. Biol. 399:436–49
    [Google Scholar]
  84. Johnston RJ, Comps-Agrar L, Hackney J, Yu X, Huseni M et al. 2014. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell 26:923–37
    [Google Scholar]
  85. Kang L, Voskinarian-Berse V, Law E, Reddin T, Bhatia M et al. 2013. Characterization and ex vivo expansion of human placenta-derived natural killer cells for cancer immunotherapy. Front. Immunol. 4:101
    [Google Scholar]
  86. Karlhofer FM, Ribuado RK, Yokoyama WM 1992. MHC class I alloantigen specificity of Ly-49+ IL-2- activated natural killer cells. Nature 358:66–70
    [Google Scholar]
  87. Karre K, Ljunggren HG, Piontek G, Kiessling R 1986. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defense strategy. Nature 319:675–78
    [Google Scholar]
  88. Kellner C, Bruenke J, Horner H, Schubert J, Schwenkert M et al. 2011. Heterodimeric bispecific antibody-derivatives against CD19 and CD16 induce effective antibody-dependent cellular cytotoxicity against B-lymphoid tumor cells. Cancer Lett 303:128–39
    [Google Scholar]
  89. Kellner C, Bruenke J, Stieglmaier J, Schwemmlein M, Schwenkert M et al. 2008. A novel CD19-directed recombinant bispecific antibody derivative with enhanced immune effector functions for human leukemic cells. J. Immunother. 31:871–84
    [Google Scholar]
  90. Kiessling R, Klein E, 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. 5:112–17
    [Google Scholar]
  91. Kipriyanov SM, Cochlovius B, Schafer HJ, Moldenhauer G, Bahre A et al. 2002. Synergistic antitumor effect of bispecific CD19×CD3 and CD19×CD16 diabodies in a preclinical model of non-Hodgkin's lymphoma. J. Immunol. 169:137–44
    [Google Scholar]
  92. Klose CS, Artis D 2016. Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis. Nat. Immunol. 17:765–74
    [Google Scholar]
  93. Knorr DA, Kaufman DS 2010. Pluripotent stem cell-derived natural killer cells for cancer therapy. Transl. Res. 156:147–54
    [Google Scholar]
  94. Kohrt HE, Colevas AD, Houot R, Weiskopf K, Goldstein MJ et al. 2014. Targeting CD137 enhances the efficacy of cetuximab. J. Clin. Investig. 124:2668–82
    [Google Scholar]
  95. Kohrt HE, Houot R, Goldstein MJ, Weiskopf K, Alizadeh AA et al. 2011. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. Blood 117:2423–32
    [Google Scholar]
  96. Kohrt HE, Houot R, Weiskopf K, Goldstein MJ, Scheeren F et al. 2012. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J. Clin. Investig. 122:1066–75
    [Google Scholar]
  97. Kugler M, Stein C, Kellner C, Mentz K, Saul D et al. 2010. A recombinant trispecific single-chain Fv derivative directed against CD123 and CD33 mediates effective elimination of acute myeloid leukaemia cells by dual targeting. Br. J. Haematol. 150:574–86
    [Google Scholar]
  98. Kurosaki T, Ravetch JV 1989. A single amino acid in the glycosyl phosphatidylinositol attachment domain determines the membrane topology of FcγRIII. Nature 342:805–7
    [Google Scholar]
  99. Lajoie L, Congy-Jolivet N, Bolzec A, Gouilleux-Gruart V, Sicard E et al. 2013. ADAM17-mediated shedding of FcγRIIIA on human NK cells: identification of the cleavage site and relationship with activation. J. Immunol. 192:2741–51
    [Google Scholar]
  100. Lanier LL. 2005. NK cell recognition. Annu. Rev. Immunol. 23:225–74
    [Google Scholar]
  101. Lanier LL. 2009. DAP10- and DAP12-associated receptors in innate immunity. Immunol. Rev. 227:150–60
    [Google Scholar]
  102. Lanier LL. 2015. NKG2D and its ligands in host defense. Cancer Immunol. Res. 3:575–82
    [Google Scholar]
  103. Lanier LL, Yu G, Phillips JH 1989. Co-association of CD3ζ with a receptor (CD16) for IgG Fc on human natural killer cells. Nature 342:803–5
    [Google Scholar]
  104. Lee J, Zhang T, Hwang I, Kim A, Nitschke L et al. 2015. Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals. Immunity 42:431–42
    [Google Scholar]
  105. Lee N, Llano M, Carretero M, Ishitani A, Navarro F et al. 1998. HLA-E is a major ligand for the NK inhibitory receptor CD94/NKG2A. PNAS 95:5199–204
    [Google Scholar]
  106. Liu B, Kong L, Han K, Hong H, Marcus WD et al. 2016. A novel fusion of ALT-803 (interleukin (IL)-15 superagonist) with an antibody demonstrates antigen-specific antitumor responses. J. Biol. Chem. 291:23869–81
    [Google Scholar]
  107. Liu E, Tong Y, Dotti G, Shaim H, Savoldo B et al. 2018. Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity. Leukemia 32:520–31
    [Google Scholar]
  108. Lopez-Soto A, Gonzalez S, Smyth MJ, Galluzzi L 2017. Control of metastasis by NK cells. Cancer Cell 32:135–54
    [Google Scholar]
  109. Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA 1981. Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 41:4420–25
    [Google Scholar]
  110. Luetke-Eversloh M, Hammer Q, Durek P, Nordstrom K, Gasparoni G et al. 2014. Human cytomegalovirus drives epigenetic imprinting of the IFNG locus in NKG2Chi natural killer cells. PLOS Pathog 10:e1004441
    [Google Scholar]
  111. Malmberg KJ, Carlsten M, Bjorklund A, Sohlberg E, Bryceson YT, Ljunggren HG 2017. Natural killer cell-mediated immunosurveillance of human cancer. Semin. Immunol. 31:20–29
    [Google Scholar]
  112. Matta J, Baratin M, Chiche L, Forel JM, Cognet C et al. 2013. Induction of B7-H6, a ligand for the natural killer cell–activating receptor NKp30, in inflammatory conditions. Blood 122:394–404
    [Google Scholar]
  113. McWilliams EM, Mele JM, Cheney C, Timmerman EA, Fiazuddin F et al. 2016. Therapeutic CD94/NKG2A blockade improves natural killer cell dysfunction in chronic lymphocytic leukemia. Oncoimmunology 5:e1226720
    [Google Scholar]
  114. Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA et al. 1997. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat. Med. 3:682–85
    [Google Scholar]
  115. Miller JS, Morishima C, McNeel DG, Patel MR, Kohrt HEK et al. 2018. A first-in-human phase I study of subcutaneous outpatient recombinant human IL15 (rhIL15) in adults with advanced solid tumors. Clin. Cancer Res. 24:1525–35
    [Google Scholar]
  116. Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH et al. 2005. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105:3051–57
    [Google Scholar]
  117. Miller JS, Tessmer-Tuck J, Pierson BA, Weisdorf D, McGlave P et al. 1997. Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity. Biol. Blood Marrow Transplant. 3:34–44
    [Google Scholar]
  118. Mingari MC, Ponte M, Bertone S, Schiavetti F, Vitale C et al. 1998. HLA class I-specific inhibitory receptors in human T lymphocytes: interleukin-15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells. PNAS 95:1172–77
    [Google Scholar]
  119. Miyazaki T, Dierich A, Benoist C, Mathis D 1996. Independent modes of natural killing distinguished in mice lacking Lag3. Science 272:405–8
    [Google Scholar]
  120. Moore GL, Bautista C, Pong E, Nguyen DH, Jacinto J et al. 2011. A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens. mAbs 3:546–57
    [Google Scholar]
  121. Mortier E, Woo T, Advincula R, Gozalo S, Ma A 2008. IL-15Rα chaperones IL-15 to stable dendritic cell membrane complexes that activate NK cells via trans presentation. J. Exp. Med. 205:1213–25
    [Google Scholar]
  122. Morvan MG, Lanier LL 2016. NK cells and cancer: you can teach innate cells new tricks. Nat. Rev. Cancer 16:7–19
    [Google Scholar]
  123. Ndhlovu LC, Lopez-Verges S, Barbour JD, Jones RB, Jha AR et al. 2012. Tim–3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood 119:3734–43
    [Google Scholar]
  124. Ni J, Miller M, Stojanovic A, Garbi N, Cerweka A 2012. Sustained effector function of IL-12/15/18–preactivated NK cells against established tumors. J. Exp. Med. 209:2351–65
    [Google Scholar]
  125. O'Sullivan TE, Sun JC, Lanier LL 2015. Natural killer cell memory. Immunity 43:634–45
    [Google Scholar]
  126. Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A et al. 1995. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature 378:88–91
    [Google Scholar]
  127. Orr MT, Lanier LL 2010. Inhibitory Ly49 receptors on mouse natural killer cells. Curr. Top. Microbiol. Immunol. 350:67–87
    [Google Scholar]
  128. Ortaldo JR, Oldham RK, Cannon GC, Herberman RB 1977. Specificity of natural cytotoxic reactivity of normal human lymphocytes against a myeloid leukemia cell line. J. Natl. Cancer Inst. 59:77–82
    [Google Scholar]
  129. Oyer JL, Pandey V, Igarashi RY, Somanchi SS, Zakari A et al. 2016. Natural killer cells stimulated with PM21 particles expand and biodistribute in vivo: clinical implications for cancer treatment. Cytotherapy 18:653–63
    [Google Scholar]
  130. Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R et al. 1999. Identification and molecular characterization of NKP30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J. Exp. Med. 190:1505–16
    [Google Scholar]
  131. Pesce S, Greppi M, Tabellini G, Rampinelli F, Parolini S et al. 2017. Identification of a subset of human natural killer cells expressing high levels of programmed death 1: a phenotypic and functional characterization. J. Allergy Clin. Immunol. 139:335–46.e3
    [Google Scholar]
  132. Pessino A, Sivori S, Bottino C, Malaspina A, Morelli L et al. 1998. Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity. J. Exp. Med. 188:953–60
    [Google Scholar]
  133. Portner LM, Schonberg K, Hejazi M, Brunnert D, Neumann F et al. 2012. T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells following binding of bispecific tetravalent antibody CD19×CD3 or CD19×CD16. Cancer Immunol. Immunother. 61:1869–75
    [Google Scholar]
  134. Prlic M, Lefrancois L, Jameson SC 2002. Multiple choices: regulation of memory CD8 T cell generation and homeostasis by interleukin (IL)-7 and IL-15. J. Exp. Med. 195:F49–52
    [Google Scholar]
  135. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C et al. 2011. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 332:600–3
    [Google Scholar]
  136. Raulet DH, Gasser S, Gowen BG, Deng W, Jung H 2013. Regulation of ligands for the NKG2D activating receptor. Annu. Rev. Immunol. 31:413–41
    [Google Scholar]
  137. Ravetch JV, Lanier LL 2000. Immune inhibitory receptors. Science 290:84–89
    [Google Scholar]
  138. Reiners KS, Kessler J, Sauer M, Rothe A, Hansen HP et al. 2013. Rescue of impaired NK cell activity in Hodgkin lymphoma with bispecific antibodies in vitro and in patients. Mol. Ther. 21:895–903
    [Google Scholar]
  139. Renner C, Hartmann F, Jung W, Deisting C, Juwana M, Pfreundschuh M 2000. Initiation of humoral and cellular immune responses in patients with refractory Hodgkin's disease by treatment with an anti-CD16/CD30 bispecific antibody. Cancer Immunol. Immunother. 49:173–80
    [Google Scholar]
  140. Renner C, Hartmann F, Pfreundschuh M 1997. Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody. Cancer Immunol. Immunother. 45:184–86
    [Google Scholar]
  141. Renner C, Pfreundschuh M 1995. Treatment of heterotransplanted Hodgkin's tumors in SCID mice by a combination of human NK or T cells and bispecific antibodies. J. Hematother. 4:447–51
    [Google Scholar]
  142. Romagne F, Andre P, Spee P, Zahn S, Anfossi N et al. 2009. Preclinical characterization of 1–7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood 114:2667–77
    [Google Scholar]
  143. Romee R, Cooley S, Berrien-Elliott MM, Westervelt P, Verneris MR et al. 2018. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood 131:2515–27
    [Google Scholar]
  144. Romee R, Foley B, Lenvik T, Wang Y, Zhang B et al. 2013. NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17). Blood 121:3599–608
    [Google Scholar]
  145. Romee R, Rosario M, Berrien-Elliott MM, Wagner JA, Jewell BA et al. 2016. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci. Transl. Med. 8:357ra123
    [Google Scholar]
  146. Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR et al. 2012. Cytokine activation induces human memory-like NK cells. Blood 120:4751–60
    [Google Scholar]
  147. Rosen DB, Araki M, Hamerman JA, Chen T, Yamamura T, Lanier LL 2004. A structural basis for the association of DAP12 with mouse, but not human, NKG2D. J. Immunol. 173:2470–78
    [Google Scholar]
  148. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP et al. 1987. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N. Engl. J. Med. 316:889–97
    [Google Scholar]
  149. Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwarz SL 1985. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J. Exp. Med. 161:1169–88
    [Google Scholar]
  150. Rothe A, Sasse S, Topp MS, Eichenauer DA, Hummel H et al. 2015. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood 125:4024–31
    [Google Scholar]
  151. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD et al. 2002. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–100
    [Google Scholar]
  152. Ruggeri L, Urbani E, Andre P, Mancusi A, Tosti A et al. 2016. Effects of anti-NKG2A antibody administration on leukemia and normal hematopoietic cells. Haematologica 101:626–33
    [Google Scholar]
  153. Saez-Borderias A, Romo N, Magri G, Guma M, Angulo A, Lopez-Botet M 2009. IL-12-dependent inducible expression of the CD94/NKG2A inhibitory receptor regulates CD94/NKG2C+ NK cell function. J. Immunol. 182:829–36
    [Google Scholar]
  154. Sahin U, Kraft-Bauer S, Ohnesorge S, Pfreundschuh M, Renner C 1996. Interleukin-12 increases bispecific-antibody-mediated natural killer cell cytotoxicity against human tumors. Cancer Immunol. Immunother. 42:9–14
    [Google Scholar]
  155. Sarhan D, Cichocki F, Zhang B, Yingst A, Spellman SR et al. 2016. Adaptive NK cells with low TIGIT expression are inherently resistant to myeloid-derived suppressor cells. Cancer Res 76:5696–706
    [Google Scholar]
  156. Schlenzka J, Moehler TM, Kipriyanov SM, Kornacker M, Benner A et al. 2004. Combined effect of recombinant CD19×CD16 diabody and thalidomide in a preclinical model of human B cell lymphoma. Anticancer Drugs 15:915–19
    [Google Scholar]
  157. Schlums H, Cichocki F, Tesi B, Theorell J, Beziat V et al. 2015. Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function. Immunity 42:443–56
    [Google Scholar]
  158. Schmohl JU, Felices M, Oh F, Lenvik AJ, Lebeau AM et al. 2017. Engineering of anti-CD133 tri-specific molecule capable of inducing NK expansion and driving antibody-dependent cell-mediated cytotoxicity (ADCC). Cancer Res. Treat. 49:41140–52
    [Google Scholar]
  159. Schmohl JU, Felices M, Todhunter D, Taras E, Miller JS, Vallera DA 2016. Tetraspecific scFv construct provides NK cell mediated ADCC and self-sustaining stimuli via insertion of IL-15 as a cross-linker. Oncotarget 7:73830–44
    [Google Scholar]
  160. Schubert I, Kellner C, Stein C, Kugler M, Schwenkert M et al. 2011. A single-chain triplebody with specificity for CD19 and CD33 mediates effective lysis of mixed lineage leukemia cells by dual targeting. mAbs 3:21–30
    [Google Scholar]
  161. Schubert I, Kellner C, Stein C, Kugler M, Schwenkert M et al. 2012. A recombinant triplebody with specificity for CD19 and HLA-DR mediates preferential binding to antigen double-positive cells by dual-targeting. mAbs 4:45–56
    [Google Scholar]
  162. Seillet C, Belz GT, Huntington ND 2016. Development, homeostasis, and heterogeneity of NK cells and ILC1. Curr. Top. Microbiol. Immunol. 395:37–61
    [Google Scholar]
  163. Sharpe AH, Pauken KE 2018. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol. 18:153–67
    [Google Scholar]
  164. Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K et al. 1996. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4:573–81
    [Google Scholar]
  165. Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T 1994. Structure and chromosomal localization of the human PD-1 gene (PDCD1). Genomics 23:704–6
    [Google Scholar]
  166. Shiroishi M, Kuroki K, Ose T, Rasubala L, Shiratori I et al. 2006. Efficient leukocyte Ig-like receptor signaling and crystal structure of disulfide-linked HLA-G dimer. J. Biol. Chem. 281:10439–47
    [Google Scholar]
  167. Silla LM, Chen J, Zhong RK, Whiteside TL, Ball ED 1995. Potentiation of lysis of leukaemia cells by a bispecific antibody to CD33 and CD16 (FcγRIII) expressed by human natural killer (NK) cells. Br. J. Haematol. 89:712–18
    [Google Scholar]
  168. Singer H, Kellner C, Lanig H, Aigner M, Stockmeyer B et al. 2010. Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16. J. Immunother. 33:599–608
    [Google Scholar]
  169. Sitrin J, Ring A, Garcia KC, Benoist C, Mathis D 2013. Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J. Exp. Med. 210:1153–65
    [Google Scholar]
  170. Smits NC, Coupet TA, Godbersen C, Sentman CL 2016. Designing multivalent proteins based on natural killer cell receptors and their ligands as immunotherapy for cancer. Expert Opin. Biol. Ther. 16:1105–12
    [Google Scholar]
  171. Soiffer RJ, Murray C, Gonin R, Ritz J 1994. Effect of low-dose interleukin-2 on disease relapse after T-cell-depleted allogeneic bone marrow transplantation. Blood 84:964–71
    [Google Scholar]
  172. Soto EO, Pecht I 1988. A monoclonal antibody that inhibits secretion from rat basophilic leukemia cells and binds to a novel membrane component. J. Immunol. 141:4324–32
    [Google Scholar]
  173. Spits H, Bernink JH, Lanier L 2016. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat. Immunol. 17:758–64
    [Google Scholar]
  174. Stengel KF, Harden-Bowles K, Yu X, Rouge L, Yin J et al. 2012. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell–cell adhesion and signaling mechanism that requires cis-trans receptor clustering. PNAS 109:5399–404
    [Google Scholar]
  175. Stojanovic A, Fiegler N, Brunner-Weinzierl M, Cerwenka A 2014. CTLA-4 is expressed by activated mouse NK cells and inhibits NK cell IFN-γ production in response to mature dendritic cells. J. Immunol. 192:4184–91
    [Google Scholar]
  176. Strauss-Albee DM, Fukuyama J, Liang EC, Yao Y, Jarrell JA et al. 2015. Human NK cell repertoire diversity reflects immune experience and correlates with viral susceptibility. Sci. Transl. Med. 7:297ra115
    [Google Scholar]
  177. Strauss-Albee DM, Horowitz A, Parham P, Blish CA 2014. Coordinated regulation of NK receptor expression in the maturing human immune system. J. Immunol. 193:4871–79
    [Google Scholar]
  178. Sun JC, Beilke JN, Lanier LL 2009. Adaptive immune features of natural killer cells. Nature 457:557–61
    [Google Scholar]
  179. Sun JC, Lanier LL 2011. NK cell development, homeostasis and function: parallels with CD8 T cells. Nat. Rev. Immunol. 11:645–57
    [Google Scholar]
  180. Sun JC, Madera S, Bezman NA, Beilke JN, Kaplan MH, Lanier LL 2012. Proinflammatory cytokine signaling required for the generation of natural killer cell memory. J. Exp. Med. 215:947–54
    [Google Scholar]
  181. Tahara-Hanaoka S, Shibuya K, Kai H, Miyamoto A, Morikawa Y et al. 2005. Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor. Blood 107:1491–96
    [Google Scholar]
  182. Tahara-Hanaoka S, Shibuya K, Onoda Y, Zhang H, Yamazaki S et al. 2004. Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). Int. Immunol. 16:533–38
    [Google Scholar]
  183. Tessmer MS, Fugere C, Stevenaert F, Naidenko OV, Chong HJ et al. 2007. KLRG1 binds cadherins and preferentially associates with SHIP-1. Int. Immunol. 19:391–400
    [Google Scholar]
  184. Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S et al. 2015. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16:57–66
    [Google Scholar]
  185. Triebel F, Jisukawa S, Baixeras E, Roman-Roman S, Genevee C et al. 1990. LAG-3, a novel lymphocyte activation gene closely related to CD4. J. Exp. Med. 171:1393–405
    [Google Scholar]
  186. Upshaw JL, Arneson LN, Schoon RA, Dick CJ, Billadeau DD, Leibson PJ 2006. NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells. Nat. Immunol. 7:524–32
    [Google Scholar]
  187. Vallera DA, Felices M, McElmurry R, McCullar V, Zhou X et al. 2016. IL15 trispecific Killer engagers (TriKE) make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin. Cancer Res. 22:3440–50
    [Google Scholar]
  188. Vallera DA, Zhang B, Gleason MK, Oh S, Weiner LM et al. 2013. Heterodimeric bispecific single-chain variable-fragment antibodies against EpCAM and CD16 induce effective antibody-dependent cellular cytotoxicity against human carcinoma cells. Cancer Biother. Radiopharm. 28:4274–82
    [Google Scholar]
  189. Vance RE, Kraft JR, Altman JD, Jensen PE, Raulet DH 1998. Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical major histocompatibility complex (MHC) class I molecule Qa-1b. J. Exp. Med. 188:1841–48
    [Google Scholar]
  190. Vey N, Bourhis JH, Boissel N, Bordessoule D, Prebet T et al. 2012. A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. Blood 120:4317–23
    [Google Scholar]
  191. Vitale M, Bottino C, Sivori S, Sanseverino L, Castriconi R et al. 1998. NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J. Exp. Med. 187:2065–72
    [Google Scholar]
  192. Voehringer D, Koschella M, Pircher H 2002. Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1). Blood 100:3698–702
    [Google Scholar]
  193. von Strandmann EP, Hansen HP, Reiners KS, Schnell R, Borchmann P et al. 2006. A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo. Blood 107:1955–62
    [Google Scholar]
  194. Wagtmann N, Biassoni R, Cantoni C, Verdiani S, Malnati MS et al. 1995. Molecular clones of the p58 natural killer cell receptor reveal Ig-related molecules with diversity in both the extra- and intracellular domains. Immunity 2:439–49
    [Google Scholar]
  195. Waldmann T, Tagaya Y, Bamford R 1998. Interleukin-2, interleukin-15, and their receptors. Int. Rev. Immunol. 16:205–26
    [Google Scholar]
  196. Weiner LM, Clark JI, Davey M, Li WS, Garcia de Palazzo I et al. 1995.a Phase I trial of 2B1, a bispecific monoclonal antibody targeting c-erbB-2 and FcγRIII. Cancer Res 55:4586–93
    [Google Scholar]
  197. Weiner LM, Clark JI, Ring DB, Alpaugh RK 1995.b Clinical development of 2B1, a bispecific murine monoclonal antibody targeting c-erbB-2 and FcγRIII. J. Hematother. 4:453–56
    [Google Scholar]
  198. Weizman OE, Adams NM, Schuster IS, Krishna C, Pritykin Y et al. 2017. ILC1 confer early host protection at initial sites of viral infection. Cell 171:795–808
    [Google Scholar]
  199. Wiernik A, Foley B, Zhang B, Verneris MR, Warlick E et al. 2013. Targeting natural killer cells to acute myeloid leukemia in vitro with a CD16×33 bispecific killer cell engager and ADAM17 inhibition. Clin. Cancer Res. 19:3844–55
    [Google Scholar]
  200. Wiesmayr S, Webber SA, Macedo C, Popescu I, Smith L et al. 2011. Decreased NKp46 and NKG2D and elevated PD-1 are associated with altered NK-cell function in pediatric transplant patients with PTLD. Eur. J. Immunol. 42:541–50
    [Google Scholar]
  201. Woll PS, Grzywacz B, Tian X, Marcus RK, Knorr DA et al. 2009. Human embryonic stem cells differentiate into a homogeneous population of natural killer cells with potent in vivo antitumor activity. Blood 113:6094–101
    [Google Scholar]
  202. Wrangle JM, Velcheti V, Patel MR, Garrett-Mayer E, Hill EG et al. 2018. ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial. Lancet Oncol 19:5694–704
    [Google Scholar]
  203. Wu J, Song Y, Bakker AB, Bauer S, Spies T et al. 1999. An activating immunoreceptor complex formed by NKG2D and DAP10. Science 285:730–32
    [Google Scholar]
  204. Wu N, Veillette A 2016. SLAM family receptors in normal immunity and immune pathologies. Curr. Opin. Immunol. 38:45–51
    [Google Scholar]
  205. Yron I, Wood TA Jr., Spiess PJ, Rosenberg SA 1980. In vitro growth of murine T cells. V. The isolation and growth of lymphoid cells infiltrating syngeneic solid tumors. J. Immunol. 125:238–45
    [Google Scholar]
  206. Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E et al. 2009. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol. 10:48–57
    [Google Scholar]
  207. Zhang T, Scott JM, Hwang I, Kim S 2013. Cutting edge: antibody-dependent memory-like NK cells distinguished by FcRγ deficiency. J. Immunol. 190:1402–6
    [Google Scholar]
  208. Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J et al. 2009. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood 114:3793–802
    [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-030518-055653
Loading
/content/journals/10.1146/annurev-cancerbio-030518-055653
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error