Skip to main content
SpringerLink
Log in

Cancer Immunosurveillance by Natural Killer Cells and Other Innate Lymphoid Cells

  • Chapter
  • First Online:
Oncoimmunology

Abstract

Natural Killer (NK) cells have long been known for their potent cytokine producing and cytotoxic capacities against transformed or infected cells. In particular, they are recognized to play an early role in immune surveillance (detection and elimination) of developing tumors (especially hematological cancers) and metastasis to distant organs. NK cells are also the first identified protagonists of a new emerging family of innate lymphoid cells (ILCs) that regulate several physiological processes such as immunity, tissue remodeling, and metabolism to maintain body integrity. NK cells express an array of receptors allowing them to sense malignant cells. NK cells exert their anti-tumor function mainly through the direct killing of the cancer cells and the secretion of the anti-tumor cytokine IFN-γ. Recently, it has been suggested that ILC subsets other than NK cells could also respond to cancer cells and play a role in anti-tumor immunity. In this chapter, we will detail the various mechanisms by which NK cells recognize and eliminate cancer cells. Moreover, we will revisit the role of NK cells in cancer immunosurveillance in light of the recent findings on the other ILC family members.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T. Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer. 2014;14(2):135–46.

    Article  CAS  PubMed  Google Scholar 

  2. Fridman WH, Galon J, Pages F, Tartour E, Sautes-Fridman C, Kroemer G. Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res. 2011;71(17):5601–5.

    Article  CAS  PubMed  Google Scholar 

  3. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.

    Article  CAS  PubMed  Google Scholar 

  4. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71.

    Article  CAS  PubMed  Google Scholar 

  5. Jaiswal S, Chao MP, Majeti R, Weissman IL. Macrophages as mediators of tumor immunosurveillance. Trends Immunol. 2010;31(6):212–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Blaisdell A, Crequer A, Columbus D, Daikoku T, Mittal K, Dey SK, Erlebacher A. Neutrophils oppose uterine epithelial carcinogenesis via debridement of hypoxic tumor cells. Cancer Cell. 2015;28(6):785–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Altman JB, Benavides AD, Das R, Bassiri H. Antitumor responses of invariant natural killer T cells. J Immunol Res. 2015;2015:652875.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Girardi M. Immunosurveillance and immunoregulation by gammadelta T cells. J Invest Dermatol. 2006;126(1):25–31.

    Article  CAS  PubMed  Google Scholar 

  9. van Beek JJP, Martens AWJ, Bakdash G, de Vries IJM. Innate lymphoid cells in tumor immunity. Biomedicine. 2016;4(7) pii E7. doi: 10.3390/biomedicines4010007.

    Google Scholar 

  10. Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F, Vivier E. Innate lymphoid cells–a proposal for uniform nomenclature. Nat Rev Immunol. 2013;13(2):145–9.

    Article  CAS  PubMed  Google Scholar 

  11. Zook EC, Kee BL. Development of innate lymphoid cells. Nat Immunol. 2016;17(7):775–82.

    Article  CAS  PubMed  Google Scholar 

  12. Eberl G, Di Santo JP, Vivier E. The brave new world of innate lymphoid cells. Nat Immunol. 2015;16(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  13. Dadi S, Chhangawala S, Whitlock BM, Franklin RA, Luo CT, Oh SA, Toure A, Pritykin Y, Huse M, Leslie CS, Li MO. Cancer immunosurveillance by tissue-resident innate lymphoid cells and innate-like T cells. Cell. 2016;164(3):365–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, Iwakura Y, Yagita H, Okumura K. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med. 2001;7(1):94–100.

    Article  CAS  PubMed  Google Scholar 

  15. Klose CS, Flach M, Mohle L, Rogell L, Hoyler T, Ebert K, Fabiunke C, Pfeifer D, Sexl V, Fonseca-Pereira D, Domingues RG, Veiga-Fernandes H, Arnold SJ, Busslinger M, Dunay IR, Tanriver Y, Diefenbach A. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell. 2014;157(2):340–56.

    Article  CAS  PubMed  Google Scholar 

  16. Spits H, Bernink JH, Lanier L. NK cells and type 1 innate lymphoid cells: partners in host defense. Nat Immunol. 2016;17(7):758–64.

    Article  CAS  PubMed  Google Scholar 

  17. Seillet C, Belz GT, Huntington ND. Development, homeostasis, and heterogeneity of NK cells and ILC1. Curr Top Microbiol Immunol. 2016;395:37–61.

    PubMed  Google Scholar 

  18. Cortez VS, Cervantes-Barragan L, Robinette ML, Bando JK, Wang Y, Geiger TL, Gilfillan S, Fuchs A, Vivier E, Sun JC, Cella M, Colonna M. Transforming growth factor-beta signaling guides the differentiation of innate lymphoid cells in salivary glands. Immunity. 2016;44(5):1127–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kiessling R, Klein E, Wigzell H. “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. 1975;5(2):112–7.

    Article  CAS  PubMed  Google Scholar 

  20. Walzer T, Blery M, Chaix J, Fuseri N, Chasson L, Robbins SH, Jaeger S, Andre P, Gauthier L, Daniel L, Chemin K, Morel Y, Dalod M, Imbert J, Pierres M, Moretta A, Romagne F, Vivier E. Identification, activation, and selective in vivo ablation of mouse NK cells via NKp46. Proc Natl Acad Sci U S A. 2007;104(9):3384–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hayakawa Y, Huntington ND, Nutt SL, Smyth MJ. Functional subsets of mouse natural killer cells. Immunol Rev. 2006;214:47–55.

    Article  CAS  PubMed  Google Scholar 

  22. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001;22(11):633–40.

    Article  CAS  PubMed  Google Scholar 

  23. Smyth MJ, Thia KY, Cretney E, Kelly JM, Snook MB, Forbes CA, Scalzo AA. Perforin is a major contributor to NK cell control of tumor metastasis. J Immunol. 1999;162(11):6658–62.

    CAS  PubMed  Google Scholar 

  24. Smyth MJ, Crowe NY, Godfrey DI. NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol. 2001;13(4):459–63.

    Article  CAS  PubMed  Google Scholar 

  25. Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of NK cells in tumour growth and metastasis in beige mice. Nature. 1980;284(5757):622–4.

    Article  CAS  PubMed  Google Scholar 

  26. Vosshenrich CA, Ranson T, Samson SI, Corcuff E, Colucci F, Rosmaraki EE, Di Santo JP. Roles for common cytokine receptor gamma-chain-dependent cytokines in the generation, differentiation, and maturation of NK cell precursors and peripheral NK cells in vivo. J Immunol. 2005;174(3):1213–21.

    Article  CAS  PubMed  Google Scholar 

  27. Sathe P, Delconte RB, Souza-Fonseca-Guimaraes F, Seillet C, Chopin M, Vandenberg CJ, Rankin LC, Mielke LA, Vikstrom I, Kolesnik TB, Nicholson SE, Vivier E, Smyth MJ, Nutt SL, Glaser SP, Strasser A, Belz GT, Carotta S, Huntington ND. Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells. Nat Commun. 2014;5:4539.

    Article  CAS  PubMed  Google Scholar 

  28. Merzoug LB, Marie S, Satoh-Takayama N, Lesjean S, Albanesi M, Luche H, Fehling HJ, Di Santo JP, Vosshenrich CA. Conditional ablation of NKp46+ cells using a novel Ncr1(greenCre) mouse strain: NK cells are essential for protection against pulmonary B16 metastases. Eur J Immunol. 2014;44(11):3380–91.

    Article  PubMed  CAS  Google Scholar 

  29. Guillerey C, Smyth MJ. NK cells and cancer immunoediting. Curr Top Microbiol Immunol. 2016;395:115–45.

    PubMed  Google Scholar 

  30. Vallentin B, Barlogis V, Piperoglou C, Cypowyj S, Zucchini N, Chene M, Navarro F, Farnarier C, Vivier E, Vely F. Innate lymphoid cells in cancer. Cancer Immunol Res. 2015;3(10):1109–14.

    Article  CAS  PubMed  Google Scholar 

  31. Ikutani M, Yanagibashi T, Ogasawara M, Tsuneyama K, Yamamoto S, Hattori Y, Kouro T, Itakura A, Nagai Y, Takaki S, Takatsu K. Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity. J Immunol. 2012;188(2):703–13.

    Article  CAS  PubMed  Google Scholar 

  32. Kim J, Kim W, Moon UJ, Kim HJ, Choi HJ, Sin JI, Park NH, Cho HR, Kwon B. Intratumorally establishing type 2 innate lymphoid cells blocks tumor growth. J Immunol. 2016;196(5):2410–23.

    Article  CAS  PubMed  Google Scholar 

  33. Carrega P, Loiacono F, Di Carlo E, Scaramuccia A, Mora M, Conte R, Benelli R, Spaggiari GM, Cantoni C, Campana S, Bonaccorsi I, Morandi B, Truini M, Mingari MC, Moretta L, Ferlazzo G. NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures. Nat Commun. 2015;6:8280.

    Article  CAS  PubMed  Google Scholar 

  34. Eisenring M, Vom Berg J, Kristiansen G, Saller E, Becher B. IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nat Immunol. 2010;11(11):1030–8.

    Article  CAS  PubMed  Google Scholar 

  35. Mattner J, Wirtz S. Friend or foe? The ambiguous role of innate lymphoid cells in cancer development. Trends Immunol. 2017;38(1):29–38.

    Article  CAS  PubMed  Google Scholar 

  36. Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, Wang L, Shifrin N, Raulet DH. Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol. 2014;122:91–128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Newman KC, Riley EM. Whatever turns you on: accessory-cell-dependent activation of NK cells by pathogens. Nat Rev Immunol. 2007;7(4):279–91.

    Article  CAS  PubMed  Google Scholar 

  38. Ljunggren HG, Karre K. In search of the ‘missing self’: MHC molecules and NK cell recognition. Immunol Today. 1990;11(7):237–44.

    Article  CAS  PubMed  Google Scholar 

  39. Garcia-Lora A, Algarra I, Garrido F. MHC class I antigens, immune surveillance, and tumor immune escape. J Cell Physiol. 2003;195(3):346–55.

    Article  CAS  PubMed  Google Scholar 

  40. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S. Functions of natural killer cells. Nat Immunol. 2008;9(5):503–10.

    Article  CAS  PubMed  Google Scholar 

  41. Guillerey C, Huntington ND, Smyth MJ. Targeting natural killer cells in cancer immunotherapy. Nat Immunol. 2016;17(9):1025–36.

    Article  CAS  PubMed  Google Scholar 

  42. Kruse PH, Matta J, Ugolini S, Vivier E. Natural cytotoxicity receptors and their ligands. Immunol Cell Biol. 2014;92(3):221–9.

    Article  CAS  PubMed  Google Scholar 

  43. Salimi M, Xue L, Jolin H, Hardman C, Cousins DJ, McKenzie AN, Ogg GS. Group 2 innate lymphoid cells express functional NKp30 receptor inducing type 2 cytokine production. J Immunol. 2016;196(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  44. Rosental B, Brusilovsky M, Hadad U, Oz D, Appel MY, Afergan F, Yossef R, Rosenberg LA, Aharoni A, Cerwenka A, Campbell KS, Braiman A, Porgador A. Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44. J Immunol. 2011;187(11):5693–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Siewiera J, Gouilly J, Hocine HR, Cartron G, Levy C, Al-Daccak R, Jabrane-Ferrat N. Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes. Nat Commun. 2015;6:10183.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Delahaye NF, Rusakiewicz S, Martins I, Menard C, Roux S, Lyonnet L, Paul P, Sarabi M, Chaput N, Semeraro M, Minard-Colin V, Poirier-Colame V, Chaba K, Flament C, Baud V, Authier H, Kerdine-Romer S, Pallardy M, Cremer I, Peaudecerf L, Rocha B, Valteau-Couanet D, Gutierrez JC, Nunes JA, Commo F, Bonvalot S, Ibrahim N, Terrier P, Opolon P, Bottino C, Moretta A, Tavernier J, Rihet P, Coindre JM, Blay JY, Isambert N, Emile JF, Vivier E, Lecesne A, Kroemer G, Zitvogel L. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nat Med. 2011;17(6):700–7.

    Article  CAS  PubMed  Google Scholar 

  47. Halfteck GG, Elboim M, Gur C, Achdout H, Ghadially H, Mandelboim O. Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1. J Immunol. 2009;182(4):2221–30.

    Article  CAS  PubMed  Google Scholar 

  48. Glasner A, Ghadially H, Gur C, Stanietsky N, Tsukerman P, Enk J, Mandelboim O. Recognition and prevention of tumor metastasis by the NK receptor NKp46/NCR1. J Immunol. 2012;188(6):2509–15.

    Article  CAS  PubMed  Google Scholar 

  49. Raulet DH. Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol. 2003;3(10):781–90.

    Article  CAS  PubMed  Google Scholar 

  50. Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature. 2005;436(7054):1186–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature. 2001;413(6852):165–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F, Xiong N, Knoblaugh S, Cado D, Greenberg NM, Raulet DH. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity. 2008;28(4):571–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Smyth MJ, Swann J, Cretney E, Zerafa N, Yokoyama WM, Hayakawa Y. NKG2D function protects the host from tumor initiation. J Exp Med. 2005;202(5):583–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang B, Kracker S, Yasuda T, Casola S, Vanneman M, Homig-Holzel C, Wang Z, Derudder E, Li S, Chakraborty T, Cotter SE, Koyama S, Currie T, Freeman GJ, Kutok JL, Rodig SJ, Dranoff G, Rajewsky K. Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model. Cell. 2012;148(4):739–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Vitale M, Cantoni C, Pietra G, Mingari MC, Moretta L. Effect of tumor cells and tumor microenvironment on NK-cell function. Eur J Immunol. 2014;44(6):1582–92.

    Article  CAS  PubMed  Google Scholar 

  56. Jinushi M, Vanneman M, Munshi NC, Tai YT, Prabhala RH, Ritz J, Neuberg D, Anderson KC, Carrasco DR, Dranoff G. MHC class I chain-related protein a antibodies and shedding are associated with the progression of multiple myeloma. Proc Natl Acad Sci U S A. 2008;105(4):1285–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Groh V, Wu J, Yee C, Spies T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature. 2002;419(6908):734–8.

    Article  CAS  PubMed  Google Scholar 

  58. Coudert JD, Scarpellino L, Gros F, Vivier E, Held W. Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways. Blood. 2008;111(7):3571–8.

    Article  CAS  PubMed  Google Scholar 

  59. Deng W, Gowen BG, Zhang L, Wang L, Lau S, Iannello A, Xu J, Rovis TL, Xiong N, Raulet DH. Antitumor immunity. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection. Science. 2015;348(6230):136–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Martinet L, Smyth MJ. Balancing natural killer cell activation through paired receptors. Nat Rev Immunol. 2015;15(4):243–54.

    Article  CAS  PubMed  Google Scholar 

  61. Samanta D, Almo SC. Nectin family of cell-adhesion molecules: structural and molecular aspects of function and specificity. Cell Mol Life Sci. 2015;72(4):645–58.

    Article  CAS  PubMed  Google Scholar 

  62. Martinet L, Ferrari De Andrade L, Guillerey C, Lee JS, Liu J, Souza-Fonseca-Guimaraes F, Hutchinson DS, Kolesnik TB, Nicholson SE, Huntington ND, Smyth MJ. DNAM-1 expression marks an alternative program of NK cell maturation. Cell Rep. 2015;11(1):85–97.

    Article  CAS  PubMed  Google Scholar 

  63. Seillet C, Mielke LA, Amann-Zalcenstein DB, Su S, Gao J, Almeida FF, Shi W, Ritchie ME, Naik SH, Huntington ND, Carotta S, Belz GT. Deciphering the innate lymphoid cell transcriptional program. Cell Rep. 2016;17(2):436–47.

    Article  CAS  PubMed  Google Scholar 

  64. Tang ML, Gasser S. ATM activation mediates anticancer immunosurveillance by natural killer and T cells. Oncoimmunology. 2013;2(6):e24438.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Croxford JL, Tang ML, Pan MF, Huang CW, Kamran N, Phua CM, Chng WJ, Ng SB, Raulet DH, Gasser S. ATM-dependent spontaneous regression of early Emu-myc-induced murine B-cell leukemia depends on natural killer and T cells. Blood. 2013;121(13):2512–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S, Honda S, Yasui T, Kikutani H, Shibuya K, Shibuya A. Accelerated tumor growth in mice deficient in DNAM-1 receptor. J Exp Med. 2008;205(13):2959–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Gilfillan S, Chan CJ, Cella M, Haynes NM, Rapaport AS, Boles KS, Andrews DM, Smyth MJ, Colonna M. DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors. J Exp Med. 2008;205(13):2965–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Guillerey C, Ferrari de Andrade L, Vuckovic S, Miles K, Ngiow SF, Yong MC, Teng MW, Colonna M, Ritchie DS, Chesi M, Bergsagel PL, Hill GR, Smyth MJ, Martinet L. Immunosurveillance and therapy of multiple myeloma are CD226 dependent. J Clin Invest. 2015;125(5):2077–89.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Abeyweera TP, Merino E, Huse M. Inhibitory signaling blocks activating receptor clustering and induces cytoskeletal retraction in natural killer cells. J Cell Biol. 2011;192(4):675–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tu MM, Mahmoud AB, Wight A, Mottashed A, Belanger S, Rahim MM, Abou-Samra E, Makrigiannis AP. Ly49 family receptors are required for cancer immunosurveillance mediated by natural killer cells. Cancer Res. 2014;74(14):3684–94.

    Article  CAS  PubMed  Google Scholar 

  71. Yu Y, Tsang JC, Wang C, Clare S, Wang J, Chen X, Brandt C, Kane L, Campos LS, Lu L, Belz GT, McKenzie AN, Teichmann SA, Dougan G, Liu P. Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway. Nature. 2016;539(7627):102–6.

    Article  CAS  PubMed  Google Scholar 

  72. Blake SJ, Dougall WC, Miles JJ, Teng MW, Smyth MJ. Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res. 2016;22(21):5183–8.

    Article  PubMed  Google Scholar 

  73. Stanietsky N, Rovis TL, Glasner A, Seidel E, Tsukerman P, Yamin R, Enk J, Jonjic S, Mandelboim O. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur J Immunol. 2013;43(8):2138–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, Levine Z, Beiman M, Dassa L, Achdout H, Stern-Ginossar N, Tsukerman P, Jonjic S, Mandelboim O. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42):17858–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Chan CJ, Martinet L, Gilfillan S, Souza-Fonseca-Guimaraes F, Chow MT, Town L, Ritchie DS, Colonna M, Andrews DM, Smyth MJ. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 2014;15(5):431–8.

    Article  CAS  PubMed  Google Scholar 

  76. Bando JK, Colonna M. Innate lymphoid cell function in the context of adaptive immunity. Nat Immunol. 2016;17(7):783–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Yajima T, Nishimura H, Wajjwalku W, Harada M, Kuwano H, Yoshikai Y. Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response. Int J Cancer. 2002;99(4):573–8.

    Article  CAS  PubMed  Google Scholar 

  78. Smyth MJ, Swann J, Kelly JM, Cretney E, Yokoyama WM, Diefenbach A, Sayers TJ, Hayakawa Y. NKG2D recognition and perforin effector function mediate effective cytokine immunotherapy of cancer. J Exp Med. 2004;200(10):1325–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Smyth MJ, Taniguchi M, Street SE. The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol. 2000;165(5):2665–70.

    Article  CAS  PubMed  Google Scholar 

  80. Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18-preactivated NK cells against established tumors. J Exp Med. 2012;209(13):2351–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Crellin NK, Trifari S, Kaplan CD, Satoh-Takayama N, Di Santo JP, Spits H. Regulation of cytokine secretion in human CD127(+) LTi-like innate lymphoid cells by Toll-like receptor 2. Immunity. 2010;33(5):752–64.

    Article  CAS  PubMed  Google Scholar 

  82. Sivori S, Carlomagno S, Pesce S, Moretta A, Vitale M, Marcenaro E. TLR/NCR/KIR: which one to use and when? Front Immunol. 2014;5:105.

    PubMed  PubMed Central  Google Scholar 

  83. Guillerey C, Chow MT, Miles K, Olver S, Sceneay J, Takeda K, Moller A, Smyth MJ. Toll-like receptor 3 regulates NK cell responses to cytokines and controls experimental metastasis. Oncoimmunology. 2015;4(9):e1027468.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Degli-Esposti MA, Smyth MJ. Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol. 2005;5(2):112–24.

    Article  CAS  PubMed  Google Scholar 

  85. Lucas M, Schachterle W, Oberle K, Aichele P, Diefenbach A. Dendritic cells prime natural killer cells by trans-presenting interleukin 15. Immunity. 2007;26(4):503–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ganal SC, Sanos SL, Kallfass C, Oberle K, Johner C, Kirschning C, Lienenklaus S, Weiss S, Staeheli P, Aichele P, Diefenbach A. Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity. 2012;37(1):171–86.

    Article  CAS  PubMed  Google Scholar 

  87. Glatzer T, Killig M, Meisig J, Ommert I, Luetke-Eversloh M, Babic M, Paclik D, Bluthgen N, Seidl R, Seifarth C, Grone J, Lenarz M, Stolzel K, Fugmann D, Porgador A, Hauser A, Karlas A, Romagnani C. RORgammat(+) innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44. Immunity. 2013;38(6):1223–35.

    Article  CAS  PubMed  Google Scholar 

  88. Kagi D, Ledermann B, Burki K, Seiler P, Odermatt B, Olsen KJ, Podack ER, Zinkernagel RM, Hengartner H. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature. 1994;369(6475):31–7.

    Article  CAS  PubMed  Google Scholar 

  89. Voskoboinik I, Smyth MJ, Trapani JA. Perforin-mediated target-cell death and immune homeostasis. Nat Rev Immunol. 2006;6(12):940–52.

    Article  CAS  PubMed  Google Scholar 

  90. Street SE, Hayakawa Y, Zhan Y, Lew AM, MacGregor D, Jamieson AM, Diefenbach A, Yagita H, Godfrey DI, Smyth MJ. Innate immune surveillance of spontaneous B cell lymphomas by natural killer cells and gammadelta T cells. J Exp Med. 2004;199(6):879–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med. 2000;191(4):661–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. van den Broek MF, Kagi D, Zinkernagel RM, Hengartner H. Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur J Immunol. 1995;25(12):3514–6.

    Article  PubMed  Google Scholar 

  93. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief CJ, Zinkernagel RM, Hengartner H. Decreased tumor surveillance in perforin-deficient mice. J Exp Med. 1996;184(5):1781–90.

    Article  PubMed  Google Scholar 

  94. Screpanti V, Wallin RP, Grandien A, Ljunggren HG. Impact of FASL-induced apoptosis in the elimination of tumor cells by NK cells. Mol Immunol. 2005;42(4):495–9.

    Article  CAS  PubMed  Google Scholar 

  95. Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N, Yagita H, Okumura K. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J Exp Med. 2001;193(6):661–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Vujanovic NL. Role of TNF superfamily ligands in innate immunity. Immunol Res. 2011;50(2–3):159–74.

    Article  CAS  PubMed  Google Scholar 

  97. Li M, Knight DA, Smyth MJ, Stewart TJ. Sensitivity of a novel model of mammary cancer stem cell-like cells to TNF-related death pathways. Cancer Immunol Immunother. 2012;61(8):1255–68.

    Article  CAS  PubMed  Google Scholar 

  98. Takeda K, Cretney E, Hayakawa Y, Ota T, Akiba H, Ogasawara K, Yagita H, Kinoshita K, Okumura K, Smyth MJ. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood. 2005;105(5):2082–9.

    Article  CAS  PubMed  Google Scholar 

  99. Zamai L, Ahmad M, Bennett IM, Azzoni L, Alnemri ES, Perussia B. Natural killer (NK) cell-mediated cytotoxicity: differential use of TRAIL and Fas ligand by immature and mature primary human NK cells. J Exp Med. 1998;188(12):2375–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Robinette ML, Fuchs A, Cortez VS, Lee JS, Wang Y, Durum SK, Gilfillan S, Colonna M, Immunological Genome C. Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets. Nat Immunol. 2015;16(3):306–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Dunn C, Brunetto M, Reynolds G, Christophides T, Kennedy PT, Lampertico P, Das A, Lopes AR, Borrow P, Williams K, Humphreys E, Afford S, Adams DH, Bertoletti A, Maini MK. Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. J Exp Med. 2007;204(3):667–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Stegmann KA, Robertson F, Hansi N, Gill U, Pallant C, Christophides T, Pallett LJ, Peppa D, Dunn C, Fusai G, Male V, Davidson BR, Kennedy P, Maini MK. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver. Sci Rep. 2016;6:26157.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kayagaki N, Yamaguchi N, Nakayama M, Takeda K, Akiba H, Tsutsui H, Okamura H, Nakanishi K, Okumura K, Yagita H. Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells. J Immunol. 1999;163(4):1906–13.

    CAS  PubMed  Google Scholar 

  104. Johnsen AC, Haux J, Steinkjer B, Nonstad U, Egeberg K, Sundan A, Ashkenazi A, Espevik T. Regulation of APO-2 ligand/trail expression in NK cells-involvement in NK cell-mediated cytotoxicity. Cytokine. 1999;11(9):664–72.

    Article  CAS  PubMed  Google Scholar 

  105. Jungkunz-Stier I, Zekl M, Stuhmer T, Einsele H, Seggewiss-Bernhardt R. Modulation of natural killer cell effector functions through lenalidomide/dasatinib and their combined effects against multiple myeloma cells. Leuk Lymphoma. 2014;55(1):168–76.

    Article  CAS  PubMed  Google Scholar 

  106. Sheard MA, Asgharzadeh S, Liu Y, Lin TY, Wu HW, Ji L, Groshen S, Lee DA, Seeger RC. Membrane-bound TRAIL supplements natural killer cell cytotoxicity against neuroblastoma cells. J Immunother. 2013;36(5):319–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Screpanti V, Wallin RP, Ljunggren HG, Grandien A. A central role for death receptor-mediated apoptosis in the rejection of tumors by NK cells. J Immunol. 2001;167(4):2068–73.

    Article  CAS  PubMed  Google Scholar 

  108. Dupaul-Chicoine J, Arabzadeh A, Dagenais M, Douglas T, Champagne C, Morizot A, Rodrigue-Gervais IG, Breton V, Colpitts SL, Beauchemin N, Saleh M. The Nlrp3 Inflammasome suppresses colorectal cancer metastatic growth in the liver by promoting natural killer cell Tumoricidal activity. Immunity. 2015;43(4):751–63.

    Article  CAS  PubMed  Google Scholar 

  109. Cortez VS, Robinette ML, Colonna M. Innate lymphoid cells: new insights into function and development. Curr Opin Immunol. 2015;32:71–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting. Cytokine Growth Factor Rev. 2002;13(2):95–109.

    Article  CAS  PubMed  Google Scholar 

  111. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci U S A. 1998;95(13):7556–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood. 2001;97(1):192–7.

    Article  CAS  PubMed  Google Scholar 

  113. Bertazza L, Mocellin S. The dual role of tumor necrosis factor (TNF) in cancer biology. Curr Med Chem. 2010;17(29):3337–52.

    Article  CAS  PubMed  Google Scholar 

  114. Baxevanis CN, Voutsas IF, Tsitsilonis OE, Tsiatas ML, Gritzapis AD, Papamichail M. Compromised anti-tumor responses in tumor necrosis factor-alpha knockout mice. Eur J Immunol. 2000;30(7):1957–66.

    Article  CAS  PubMed  Google Scholar 

  115. Nagasaki E, Takahara A, Koido S, Sagawa Y, Aiba K, Tajiri H, Yagita H, Homma S. Combined treatment with dendritic cells and 5-fluorouracil elicits augmented NK cell-mediated antitumor activity through the tumor necrosis factor-alpha pathway. J Immunother. 2010;33(5):467–74.

    Article  CAS  PubMed  Google Scholar 

  116. Smyth MJ, Kelly JM, Baxter AG, Korner H, Sedgwick JD. An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J Exp Med. 1998;188(9):1611–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Balasa B, Yun R, Belmar NA, Fox M, Chao DT, Robbins MD, Starling GC, Rice AG. Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-alpha pathways. Cancer Immunol Immunother. 2015;64(1):61–73.

    Article  CAS  PubMed  Google Scholar 

  118. Andoniou CE, Coudert JD, Degli-Esposti MA. Killers and beyond: NK-cell-mediated control of immune responses. Eur J Immunol. 2008;38(11):2938–42.

    Article  CAS  PubMed  Google Scholar 

  119. Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115(11):2167–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. O'Sullivan T, Saddawi-Konefka R, Vermi W, Koebel CM, Arthur C, White JM, Uppaluri R, Andrews DM, Ngiow SF, Teng MW, Smyth MJ, Schreiber RD, Bui JD. Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med. 2012;209(10):1869–82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Crouse J, Xu HC, Lang PA, Oxenius A. NK cells regulating T cell responses: mechanisms and outcome. Trends Immunol. 2015;36(1):49–58.

    Article  CAS  PubMed  Google Scholar 

  122. Geldhof AB, van Ginderachter JA, Liu Y, Noel W, de Baetselier P. Ablation of NK cell function during tumor growth favors type 2-associated macrophages, leading to suppressed CTL generation. Clin Dev Immunol. 2003;10(2–4):71–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Adam C, King S, Allgeier T, Braumuller H, Luking C, Mysliwietz J, Kriegeskorte A, Busch DH, Rocken M, Mocikat R. DC-NK cell cross talk as a novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood. 2005;106(1):338–44.

    Article  CAS  PubMed  Google Scholar 

  124. Vitale M, Della Chiesa M, Carlomagno S, Pende D, Arico M, Moretta L, Moretta A. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood. 2005;106(2):566–71.

    Article  CAS  PubMed  Google Scholar 

  125. Krebs P, Barnes MJ, Lampe K, Whitley K, Bahjat KS, Beutler B, Janssen E, Hoebe K. NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses. Blood. 2009;113(26):6593–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Martin-Fontecha A, Thomsen LL, Brett S, Gerard C, Lipp M, Lanzavecchia A, Sallusto F. Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming. Nat Immunol. 2004;5(12):1260–5.

    Article  CAS  PubMed  Google Scholar 

  127. Roy S, Barnes PF, Garg A, Wu S, Cosman D, Vankayalapati R. NK cells lyse T regulatory cells that expand in response to an intracellular pathogen. J Immunol. 2008;180(3):1729–36.

    Article  CAS  PubMed  Google Scholar 

  128. Kelly JM, Darcy PK, Markby JL, Godfrey DI, Takeda K, Yagita H, Smyth MJ. Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol. 2002;3(1):83–90.

    Article  CAS  PubMed  Google Scholar 

  129. Schuster IS, Coudert JD, Andoniou CE, Degli-Esposti MA. “Natural regulators”: NK cells as modulators of T cell immunity. Front Immunol. 2016;7:235.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Moskalenko M, Pan M, Fu Y, de Moll EH, Hashimoto D, Mortha A, Leboeuf M, Jayaraman P, Bernardo S, Sikora AG, Wolchok J, Bhardwaj N, Merad M, Saenger Y. Requirement for innate immunity and CD90(+) NK1.1(−) lymphocytes to treat established melanoma with chemo-immunotherapy. Cancer Immunol Res. 2015;3(3):296–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, Rabbe N, Laurans L, Tartour E, de Chaisemartin L, Lebecque S, Fridman WH, Cadranel J. Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol. 2008;26(27):4410–7.

    Article  CAS  PubMed  Google Scholar 

  132. Gasteiger G, Fan X, Dikiy S, Lee SY, Rudensky AY. Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science. 2015;350(6263):981–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Vely F, Barlogis V, Vallentin B, Neven B, Piperoglou C, Ebbo M, Perchet T, Petit M, Yessaad N, Touzot F, Bruneau J, Mahlaoui N, Zucchini N, Farnarier C, Michel G, Moshous D, Blanche S, Dujardin A, Spits H, Distler JH, Ramming A, Picard C, Golub R, Fischer A, Vivier E. Evidence of innate lymphoid cell redundancy in humans. Nat Immunol. 2016;17(11):1291–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K. Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet. 2000;356(9244):1795–9.

    Article  CAS  PubMed  Google Scholar 

  135. Remark R, Alifano M, Cremer I, Lupo A, Dieu-Nosjean MC, Riquet M, Crozet L, Ouakrim H, Goc J, Cazes A, Flejou JF, Gibault L, Verkarre V, Regnard JF, Pages ON, Oudard S, Mlecnik B, Sautes-Fridman C, Fridman WH, Damotte D. Characteristics and clinical impacts of the immune environments in colorectal and renal cell carcinoma lung metastases: influence of tumor origin. Clin Cancer Res. 2013;19(15):4079–91.

    Article  CAS  PubMed  Google Scholar 

  136. Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, Andre P, Dieu-Nosjean MC, Alifano M, Regnard JF, Fridman WH, Sautes-Fridman C, Cremer I. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 2011;71(16):5412–22.

    Article  CAS  PubMed  Google Scholar 

  137. Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, Dwyer K, Stagg J, Smyth MJ, Darcy PK. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A. 2013;110(36):14711–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Viel S, Marcais A, Guimaraes FS, Loftus R, Rabilloud J, Grau M, Degouve S, Djebali S, Sanlaville A, Charrier E, Bienvenu J, Marie JC, Caux C, Marvel J, Town L, Huntington ND, Bartholin L, Finlay D, Smyth MJ, Walzer T. TGF-beta inhibits the activation and functions of NK cells by repressing the mTOR pathway. Sci Signal. 2016;9(415):ra19.

    Article  PubMed  CAS  Google Scholar 

  139. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097–100.

    Article  CAS  PubMed  Google Scholar 

  140. Kirchberger S, Royston DJ, Boulard O, Thornton E, Franchini F, Szabady RL, Harrison O, Powrie F. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J Exp Med. 2013;210(5):917–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Irshad S, Flores-Borja F, Lawler K, Monypenny J, Evans R, Male V, Gordon P, Cheung A, Gazinska P, Noor F, Wong F, Grigoriadis A, Fruhwirth G, Barber PR, Woodman N, Patel D, Rodriguez-Justo M, Owen J, Martin SG, Pinder S, Gillett C, Poland SP, Ameer-Beg S, McCaughan F, Carlin L, Hasan U, Withers DR, Lane P, Vojnovic B, Quezada SA, Ellis P, Tutt AN, Ng T. RORgammat+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Res. 2017;(77):1083–96.

    Google Scholar 

  142. Bal SM, Bernink JH, Nagasawa M, Groot J, Shikhagaie MM, Golebski K, van Drunen CM, Lutter R, Jonkers RE, Hombrink P, Bruchard M, Villaudy J, Munneke JM, Fokkens W, Erjefalt JS, Spits H, Ros XR. IL-1beta, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs. Nat Immunol. 2016;17(6):636–45.

    Article  CAS  PubMed  Google Scholar 

  143. Huang Y, Guo L, Qiu J, Chen X, Hu-Li J, Siebenlist U, Williamson PR, Urban JF Jr, Paul WE. IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential 'inflammatory' type 2 innate lymphoid cells. Nat Immunol. 2015;16(2):161–9.

    Article  CAS  PubMed  Google Scholar 

  144. Bernink JH, Peters CP, Munneke M, te Velde AA, Meijer SL, Weijer K, Hreggvidsdottir HS, Heinsbroek SE, Legrand N, Buskens CJ, Bemelman WA, Mjosberg JM, Spits H. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat Immunol. 2013;14(3):221–9.

    Article  CAS  PubMed  Google Scholar 

  145. Trabanelli S, Curti A, Lecciso M, Salome B, Riether C, Ochsenbein A, Romero P, Jandus C. CD127+ innate lymphoid cells are dysregulated in treatment naive acute myeloid leukemia patients at diagnosis. Haematologica. 2015;100(7):e257–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Hamid O, Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, Dronca R, Gangadhar TC, Patnaik A, Zarour H, Joshua AM, Gergich K, Elassaiss-Schaap J, Algazi A, Mateus C, Boasberg P, Tumeh PC, Chmielowski B, Ebbinghaus SW, Li XN, Kang SP, Ribas A. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med. 2013;369(2):134–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Kellner C, Hallack D, Glorius P, Staudinger M, Mohseni Nodehi S, de Weers M, van de Winkel JG, Parren PW, Stauch M, Valerius T, Repp R, Humpe A, Gramatzki M, Peipp M. Fusion proteins between ligands for NKG2D and CD20-directed single-chain variable fragments sensitize lymphoma cells for natural killer cell-mediated lysis and enhance antibody-dependent cellular cytotoxicity. Leukemia. 2012;26(4):830–4.

    Article  CAS  PubMed  Google Scholar 

  148. Romee R, Leong JW, Fehniger TA. Utilizing cytokines to function-enable human NK cells for the immunotherapy of cancer. Scientifica (Cairo). 2014;2014:205796.

    PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors wish to thank past and present members of the Immunology in Cancer and Infection Laboratory.

C.G. is supported by a National Health and Medical Research Council (NH&MRC) of Australia Early Career Fellowship (1107417) and a Project grant from Cure Cancer Australia (1122183). M. J. S. is supported by a NH&MRC Senior Principal Research Fellowship (1078671) and Project Grant (1098960).

Conflict of Interest

M.J. S. has contract research agreements with Bristol Myers Squibb, Aduro Biotech, Corvus Pharmaceuticals, and Medimmune. M. J. S. is an advisory board member for Arcus Biosciences, Astrazeneca, Kymab, and F-star. C.G. declares no conflict of interest.

Author information

Authors and Affiliations

  1. Immunology of Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia

    Camille Guillerey & Mark J. Smyth

  2. School of Medicine, University of Queensland, Herston, QLD, Australia

    Camille Guillerey & Mark J. Smyth

Authors
  1. Camille Guillerey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark J. Smyth
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark J. Smyth .

Editor information

Editors and Affiliations

  1. Gustave Roussy Cancer Center , Villejuif Cedex, France

    Laurence Zitvogel

  2. Gustave Roussy Cancer Center , Villejuif Cedex, France

    Guido Kroemer

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Guillerey, C., Smyth, M.J. (2018). Cancer Immunosurveillance by Natural Killer Cells and Other Innate Lymphoid Cells. In: Zitvogel, L., Kroemer, G. (eds) Oncoimmunology. Springer, Cham. https://doi.org/10.1007/978-3-319-62431-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-62431-0_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-62430-3

  • Online ISBN: 978-3-319-62431-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation