Review

The role of helper innate lymphoid cells in cancer

Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China

Search for more papers by this author

Xin Wang

*Author for correspondence: Tel.: +86 531 68776358 (B); +86 13156012606 (M); Fax: +86 531 87061197 (B);

E-mail Address: xinw@sdu.edu.cn

Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China

School of Medicine, Shandong University, Jinan, Shandong, 250012, China

Shandong Provincial Engineering Research Center of Lymphoma, Jinan, Shandong, 250021, China

Key Laboratory for Kidney Regeneration of Shandong Province, Jinan, Shandong, 250021, China

Search for more papers by this author

Published Online:26 Jun 2019https://doi.org/10.2217/imt-2019-0048

View article

Abstract

Innate lymphoid cells (ILCs) are an emerging family of innate immune cells and have been found to have an important role in infection, inflammation and tissue repair. In particular, recent work has identified significant alterations of ILC responses in tumor patients, suggesting potential roles of ILCs in tumor development. In this paper, we have focused on the basic features of ILCs and their interaction with other immune cells. Importantly, as the role of cytotoxic natural killer cells, assigned to ILC1 family, in cancer has been well established, we have summarized the new findings that showcase the potential role and mechanism of helper ILCs in different tumors. Helper ILCs might promote or inhibit tumor growth and metastasis, which depends on tumor type and ILC subset.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

Reference

1. Spits H, Artis D, Colonna M et al. Innate lymphoid cells – a proposal for uniform nomenclature. Nat. Rev. Immunol. 13(2), 145–149 (2013).Crossref, Medline, CAS, Google Scholar
2. Jeffery HC, Mcdowell P, Lutz P et al. Human intrahepatic ILC2 are IL-13positive amphiregulinpositive and their frequency correlates with model of end stage liver disease score. PLoS ONE 12(12), e0188649 (2017).Crossref, Medline, Google Scholar
3. Xu Y, Romero R, Miller D et al. Innate lymphoid cells at the human maternal-fetal interface in spontaneous preterm labor. Am. J. Reprod. Immunol. 79(6), e12820 (2018).Crossref, Medline, Google Scholar
4. Everaere L, Ait Yahia S, Boute M, Audousset C, Chenivesse C, Tsicopoulos A. Innate lymphoid cells at the interface between obesity and asthma. Immunology 153(1), 21–30 (2018).Crossref, Medline, CAS, Google Scholar
5. Wang D, Bai S, Cui Y et al. Respiratory syncytial virus prevents the subsequent development of ovalbumin-induced allergic responses by inhibiting ILC2 via the IL-33/ST2 pathway. Immunotherapy 10(12), 1065–1076 (2018).Link, CAS, Google Scholar
6. Sun JC, Lanier LL. NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat. Rev. Immunol. 11(10), 645–657 (2011).Crossref, Medline, CAS, Google Scholar
7. Shih HY, Sciume G, Poholek AC et al. Transcriptional and epigenetic networks of helper T and innate lymphoid cells. Immunol. Rev. 261(1), 23–49 (2014).Crossref, Medline, CAS, Google Scholar
8. Fuchs A, Vermi W, Lee JS et al. Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15-responsive IFN-gamma-producing cells. Immunity 38(4), 769–781 (2013).Crossref, Medline, CAS, Google Scholar
9. Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nat. Med. 21(7), 698–708 (2015).Crossref, Medline, CAS, Google Scholar
10. Diefenbach A, Colonna M, Koyasu S. Development, differentiation, and diversity of innate lymphoid cells. Immunity 41(3), 354–365 (2014).Crossref, Medline, CAS, Google Scholar
11. Hoyler T, Klose CS, Souabni A et al. The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37(4), 634–648 (2012).Crossref, Medline, CAS, Google Scholar
12. Mjosberg J, Bernink J, Golebski K et al. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37(4), 649–659 (2012).Crossref, Medline, Google Scholar
13. Cayrol C, Duval A, Schmitt P et al. Environmental allergens induce allergic inflammation through proteolytic maturation of IL-33. Nat. Immunol. 19(4), 375–385 (2018).Crossref, Medline, CAS, Google Scholar
14. Guggino G, Lin X, Rizzo A et al. IL-25 axis is involved in the pathogenesis of human primary and experimental Sjogren's syndrome. Arthritis Rheumatol. doi:10.1002/art.40500 (2018) (Epub ahead of print).Crossref, Google Scholar
15. Saenz SA, Noti M, Artis D. Innate immune cell populations function as initiators and effectors in Th2 cytokine responses. Trends Immunol. 31(11), 407–413 (2010).Crossref, Medline, CAS, Google Scholar
16. Walker JA, Mckenzie AN. Development and function of group 2 innate lymphoid cells. Curr. Opin. Immunol. 25(2), 148–155 (2013).Crossref, Medline, CAS, Google Scholar
17. Monticelli LA, Sonnenberg GF, Abt MC et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat. Immunol. 12(11), 1045–1054 (2011).Crossref, Medline, CAS, Google Scholar
18. Van De Pavert SA, Vivier E. Differentiation and function of group 3 innate lymphoid cells, from embryo to adult. Int. Immunol. 28(1), 35–42 (2016).Medline, Google Scholar
19. Cella M, Fuchs A, Vermi W et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457(7230), 722–725 (2009).Crossref, Medline, CAS, Google Scholar
20. Cupedo T, Crellin NK, Papazian N et al. Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC⁺ CD127⁺ natural killer-like cells. Nat. Immunol. 10(1), 66–74 (2009).Crossref, Medline, CAS, Google Scholar
21. Bar-Ephraim YE, Cornelissen F, Papazian N et al. Cross-tissue transcriptomic analysis of human secondary lymphoid organ-residing ILC3s reveals a quiescent state in the absence of inflammation. Cell Rep. 21(3), 823–833 (2017).Crossref, Medline, CAS, Google Scholar
22. Van De Pavert SA, Mebius RE. New insights into the development of lymphoid tissues. Nat. Rev. Immunol. 10(9), 664–674 (2010).Crossref, Medline, Google Scholar
23. Kruglov AA, Grivennikov SI, Kuprash DV et al. Nonredundant function of soluble LTalpha3 produced by innate lymphoid cells in intestinal homeostasis. Science 342(6163), 1243–1246 (2013).Crossref, Medline, CAS, Google Scholar
24. De Weerdt I, Van Hoeven V, Munneke JM et al. Innate lymphoid cells are expanded and functionally altered in chronic lymphocytic leukemia. Haematologica 101(11), e461–e464 (2016).Crossref, Medline, Google Scholar
25. Trabanelli S, Curti A, Lecciso M et al. CD127⁺ innate lymphoid cells are dysregulated in treatment naive acute myeloid leukemia patients at diagnosis. Haematologica 100(7), e257–260 (2015).Crossref, Medline, CAS, Google Scholar
26. Chevalier MF, Trabanelli S, Racle J et al. ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence. J. Clin. Invest. 127(8), 2916–2929 (2017). •• Indicates that ILC2/IL-13/MDSC axis plays a potential role in bladder cancer recurrence through in vitro experiment.Crossref, Medline, Google Scholar
27. Trabanelli S, Chevalier MF, Martinez-Usatorre A et al. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nat. Commun. 8(1), 593 (2017). •• Shows the potential role of immunosuppressive ILC2-MDSC axis in acute promyelocytic leukemia development through in vitro and in vivo experiments.Crossref, Medline, Google Scholar
28. Kini Bailur J, Mehta S, Zhang L et al. Changes in bone marrow innate lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy. Blood Adv. 1(25), 2343–2347 (2017).Crossref, Medline, Google Scholar
29. Salimi M, Wang R, Yao X et al. Activated innate lymphoid cell populations accumulate in human tumour tissues. BMC Cancer 18(1), 341 (2018).Crossref, Medline, Google Scholar
30. Pang XL, Yin TL, Yan WJ, Li J, He F, Yang J. Molecular detection of uterine innate lymphoid cells in the immunological mouse model of pregnancy loss. Int. Immunopharmacol. 68, 1–6 (2019).Crossref, Medline, CAS, Google Scholar
31. Vonarbourg C, Mortha A, Bui VL et al. Regulated expression of nuclear receptor RORgammat confers distinct functional fates to NK cell receptor-expressing RORgammat(+) innate lymphocytes. Immunity 33(5), 736–751 (2010).Crossref, Medline, CAS, Google Scholar
32. Klose CS, Kiss EA, Schwierzeck V et al. A T-bet gradient controls the fate and function of CCR6-RORgammat⁺ innate lymphoid cells. Nature 494(7436), 261–265 (2013).Crossref, Medline, CAS, Google Scholar
33. Robinette ML, Fuchs A, Cortez VS et al. Transcriptional programs define molecular characteristics of innate lymphoid cell classes and subsets. Nat. Immunol. 16(3), 306–317 (2015).Crossref, Medline, CAS, Google Scholar
34. Cella M, Otero K, Colonna M. Expansion of human NK-22 cells with IL-7, IL-2, and IL-1beta reveals intrinsic functional plasticity. Proc. Natl Acad. Sci. USA 107(24), 10961–10966 (2010).Crossref, Medline, CAS, Google Scholar
35. Bernink JH, Peters CP, Munneke M et al. Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues. Nat. Immunol. 14(3), 221–229 (2013).Crossref, Medline, CAS, Google Scholar
36. Gao Y, Souza-Fonseca-Guimaraes F, Bald T et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat. Immunol. 18(9), 1004–1015 (2017).Crossref, Medline, CAS, Google Scholar
37. Koga S, Hozumi K, Hirano KI et al. Peripheral PDGFRalpha(+)gp38(+) mesenchymal cells support the differentiation of fetal liver-derived ILC2. J. Exp. Med. 215(6), 1609–1626 (2018).Crossref, Medline, CAS, Google Scholar
38. Klose CSN, Flach M, Mohle L et al. Differentiation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157(2), 340–356 (2014).Crossref, Medline, CAS, Google Scholar
39. Sawa S, Cherrier M, Lochner M et al. Lineage relationship analysis of RORgammat⁺ innate lymphoid cells. Science 330(6004), 665–669 (2010).Crossref, Medline, CAS, Google Scholar
40. Vivier E, Artis D, Colonna M et al. Innate lymphoid cells: 10 years on. Cell 174(5), 1054–1066 (2018). • Summarizes the nomenclature of innate lymphoid cells (ILCs) and their functions in tissue homeostasis.Crossref, Medline, CAS, Google Scholar
41. Xu W, Cherrier DE, Chea S et al. An Id2(RFP)-reporter mouse redefines innate lymphoid cell precursor potentials. Immunity 50(4), 1054–1068 e1053 (2019).Crossref, Medline, CAS, Google Scholar
42. Eberl G, Colonna M, Di Santo JP, Mckenzie AN. Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science 348(6237), aaa6566 (2015).Crossref, Medline, Google Scholar
43. Crellin NK, Trifari S, Kaplan CD, Cupedo T, Spits H. Human NKp44⁺IL-22⁺ cells and LTi-like cells constitute a stable RORC⁺ lineage distinct from conventional natural killer cells. J. Exp. Med. 207(2), 281–290 (2010).Crossref, Medline, CAS, Google Scholar
44. Cherrier M, Sawa S, Eberl G. Notch, Id2, and RORgammat sequentially orchestrate the fetal development of lymphoid tissue inducer cells. J. Exp. Med. 209(4), 729–740 (2012).Crossref, Medline, CAS, Google Scholar
45. Constantinides MG, Mcdonald BD, Verhoef PA, Bendelac A. A committed precursor to innate lymphoid cells. Nature 508(7496), 397–401 (2014).Crossref, Medline, CAS, Google Scholar
46. Ishizuka IE, Chea S, Gudjonson H et al. Single-cell analysis defines the divergence between the innate lymphoid cell lineage and lymphoid tissue-inducer cell lineage. Nat. Immunol. 17(3), 269–276 (2016).Crossref, Medline, CAS, Google Scholar
47. Withers DR. Innate lymphoid cell regulation of adaptive immunity. Immunology 149(2), 123–130 (2016).Crossref, Medline, CAS, Google Scholar
48. Sciume G, Shih HY, Mikami Y, O'shea JJ. Epigenomic views of innate lymphoid cells. Front. Immunol. 8, 1579 (2017).Crossref, Medline, Google Scholar
49. Kotas ME, Locksley RM. Why innate lymphoid cells? Immunity 48(6), 1081–1090 (2018).Crossref, Medline, CAS, Google Scholar
50. Onder L, Morbe U, Pikor N et al. Lymphatic endothelial cells control initiation of lymph node organogenesis. Immunity 47(1), 80–92 e84 (2017).Crossref, Medline, CAS, Google Scholar
51. Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin. Cancer Res. 21(4), 687–692 (2015).Crossref, Medline, CAS, Google Scholar
52. Ikutani M, Yanagibashi T, Ogasawara M et al. Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity. J. Immunol. 188(2), 703–713 (2012).Crossref, Medline, CAS, Google Scholar
53. Drake LY, Iijima K, Kita H. Group 2 innate lymphoid cells and CD4⁺ T cells cooperate to mediate type 2 immune response in mice. Allergy 69(10), 1300–1307 (2014).Crossref, Medline, CAS, Google Scholar
54. Oliphant CJ, Hwang YY, Walker JA et al. MHCII-mediated dialog between group 2 innate lymphoid cells and CD4(+) T cells potentiates type 2 immunity and promotes parasitic helminth expulsion. Immunity 41(2), 283–295 (2014).Crossref, Medline, CAS, Google Scholar
55. Mirchandani AS, Besnard AG, Yip E et al. Type 2 innate lymphoid cells drive CD4⁺ Th2 cell responses. J. Immunol. 192(5), 2442–2448 (2014).Crossref, Medline, CAS, Google Scholar
56. Hardman CS, Chen YL, Salimi M et al. CD1a presentation of endogenous antigens by group 2 innate lymphoid cells. Sci. Immunol. 2(18), eaan5918 (2017).Crossref, Medline, Google Scholar
57. Reynders A, Yessaad N, Vu Manh TP et al. Identity, regulation and in vivo function of gut NKp46⁺RORgammat⁺ and NKp46⁺RORgammat^- lymphoid cells. EMBO J. 30(14), 2934–2947 (2011).Crossref, Medline, CAS, Google Scholar
58. Hepworth MR, Monticelli LA, Fung TC et al. Innate lymphoid cells regulate CD4⁺ T-cell responses to intestinal commensal bacteria. Nature 498(7452), 113–117 (2013).Crossref, Medline, CAS, Google Scholar
59. Schwartz RH. T cell anergy. Annu. Rev. Immunol. 21, 305–334 (2003).Crossref, Medline, CAS, Google Scholar
60. Molofsky AB, Van Gool F, Liang HE et al. Interleukin-33 and interferon-gamma counter-regulate group 2 innate lymphoid cell activation during immune perturbation. Immunity 43(1), 161–174 (2015).Crossref, Medline, CAS, Google Scholar
61. Krishnamoorthy N, Burkett PR, Dalli J et al. Cutting edge: maresin-1 engages regulatory T cells to limit type 2 innate lymphoid cell activation and promote resolution of lung inflammation. J. Immunol. 194(3), 863–867 (2015).Crossref, Medline, CAS, Google Scholar
62. Besnard AG, Guabiraba R, Niedbala W et al. IL-33-mediated protection against experimental cerebral malaria is linked to induction of type 2 innate lymphoid cells, M2 macrophages and regulatory T cells. PLoS Pathog. 11(2), e1004607 (2015).Crossref, Medline, Google Scholar
63. Halim TY, Steer CA, Matha L et al. Group 2 innate lymphoid cells are critical for the initiation of adaptive T helper 2 cell-mediated allergic lung inflammation. Immunity 40(3), 425–435 (2014).Crossref, Medline, CAS, Google Scholar
64. Burton OT, Medina Tamayo J, Stranks AJ et al. IgE promotes type 2 innate lymphoid cells in murine food allergy. Clin. Exp. Allergy 48(3), 288–296 (2018).Crossref, Medline, CAS, Google Scholar
65. Kim BS, Wang K, Siracusa MC et al. Basophils promote innate lymphoid cell responses in inflamed skin. J. Immunol. 193(7), 3717–3725 (2014).Crossref, Medline, CAS, Google Scholar
66. Motomura Y, Morita H, Moro K et al. Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation. Immunity 40(5), 758–771 (2014).Crossref, Medline, CAS, Google Scholar
67. Walford HH, Lund SJ, Baum RE et al. Increased ILC2s in the eosinophilic nasal polyp endotype are associated with corticosteroid responsiveness. Clin. Immunol. 155(1), 126–135 (2014).Crossref, Medline, CAS, Google Scholar
68. Doherty TA, Baum R, Newbury RO et al. Group 2 innate lymphocytes (ILC2) are enriched in active eosinophilic esophagitis. J. Allergy Clin. Immunol. 136(3), 792–794 e793 (2015).Crossref, Medline, CAS, Google Scholar
69. Johansson K, Malmhall C, Ramos-Ramirez P, Radinger M. Bone marrow type 2 innate lymphoid cells: a local source of interleukin-5 in interleukin-33-driven eosinophilia. Immunology 153(2), 268–278 (2018).Crossref, Medline, CAS, Google Scholar
70. Magri G, Miyajima M, Bascones S et al. Innate lymphoid cells integrate stromal and immunological signals to enhance antibody production by splenic marginal zone B cells. Nat. Immunol. 15(4), 354–364 (2014).Crossref, Medline, CAS, Google Scholar
71. Komlosi ZI, Kovacs N, Van De Veen W et al. Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells. J.Allergy Clin. Immunol. doi:10.1016/j.jaci.2017.07.046 (2017) (Epub ahead of print).Medline, Google Scholar
72. Mortha A, Chudnovskiy A, Hashimoto D et al. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343(6178), 1249288 (2014).Crossref, Medline, Google Scholar
73. Nakamoto N, Amiya T, Aoki R et al. Commensal lactobacillus controls immune tolerance during acute liver injury in mice. Cell Rep. 21(5), 1215–1226 (2017).Crossref, Medline, CAS, Google Scholar
74. Gerbe F, Sidot E, Smyth DJ et al. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. Nature 529(7585), 226–230 (2016).Crossref, Medline, CAS, Google Scholar
75. Howitt MR, Lavoie S, Michaud M et al. Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. Science 351(6279), 1329–1333 (2016).Crossref, Medline, CAS, Google Scholar
76. Von Moltke J, Ji M, Liang HE, Locksley RM. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529(7585), 221–225 (2016).Crossref, Medline, CAS, Google Scholar
77. Mohapatra A, Van Dyken SJ, Schneider C, Nussbaum JC, Liang HE, Locksley RM. Group 2 innate lymphoid cells utilize the IRF4-IL-9 module to coordinate epithelial cell maintenance of lung homeostasis. Mucosal Immunol. 9(1), 275–286 (2016).Crossref, Medline, CAS, Google Scholar
78. Denney L, Byrne AJ, Shea TJ et al. Pulmonary epithelial cell-derived cytokine TGF-beta1 is a critical cofactor for enhanced innate lymphoid cell function. Immunity 43(5), 945–958 (2015).Crossref, Medline, CAS, Google Scholar
79. Salimi M, Xue L, Jolin H et al. Group 2 innate lymphoid cells express functional NKp30 receptor inducing type 2 cytokine production. J. Immunol. 196(1), 45–54 (2016).Crossref, Medline, CAS, Google Scholar
80. Morita H, Kubo T, Ruckert B et al. Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid. J. Allergy Clin. Immunol. doi:10.1016/j.jaci.2018.12.1018 (2019) (Epub ahead of print).Crossref, Google Scholar
81. Nomura K, Kojima T, Fuchimoto J et al. Regulation of interleukin-33 and thymic stromal lymphopoietin in human nasal fibroblasts by proinflammatory cytokines. Laryngoscope 122(6), 1185–1192 (2012).Crossref, Medline, CAS, Google Scholar
82. De Monte L, Reni M, Tassi E et al. Intratumor T helper type 2 cell infiltrate correlates with cancer-associated fibroblast thymic stromal lymphopoietin production and reduced survival in pancreatic cancer. J. Exp. Med. 208(3), 469–478 (2011).Crossref, Medline, Google Scholar
83. Pedroza-Gonzalez A, Xu K, Wu TC et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J. Exp. Med. 208(3), 479–490 (2011).Crossref, Medline, CAS, Google Scholar
84. Munn DH, Bronte V. Immune suppressive mechanisms in the tumor microenvironment. Curr. Opin. Immunol. 39, 1–6 (2016).Crossref, Medline, CAS, Google Scholar
85. Morvan MG, Lanier LL. NK cells and cancer: you can teach innate cells new tricks. Nat. Rev. Cancer 16(1), 7–19 (2016). • Introduces the role of natural killer (NK) cells in immune surveillance against cancer and summarizes new therapeutic approaches for tumor treatment through targeting NK cells.Crossref, Medline, CAS, Google Scholar
86. Lopez-Soto A, Gonzalez S, Smyth MJ, Galluzzi L. Control of metastasis by NK cells. Cancer Cell 32(2), 135–154 (2017).Crossref, Medline, CAS, Google Scholar
87. Grossenbacher SK, Aguilar EG, Murphy WJ. Leveraging natural killer cells for cancer immunotherapy. Immunotherapy 9(6), 487–497 (2017).Link, CAS, Google Scholar
88. Bie Q, Zhang P, Su Z et al. Polarization of ILC2s in peripheral blood might contribute to immunosuppressive microenvironment in patients with gastric cancer. J. Immunol. Res. 2014, 923135 (2014).Crossref, Medline, Google Scholar
89. Saadalla AM, Osman A, Gurish MF et al. Mast cells promote small bowel cancer in a tumor stage-specific and cytokine-dependent manner. Proc. Natl Acad. Sci. USA 115(7), 1588–1592 (2018).Crossref, Medline, CAS, Google Scholar
90. Hayakawa Y, Ariyama H, Stancikova J et al. Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche. Cancer Cell 28(6), 800–814 (2015).Crossref, Medline, CAS, Google Scholar
91. Kirchberger S, Royston DJ, Boulard O et al. Innate lymphoid cells sustain colon cancer through production of interleukin-22 in a mouse model. J. Exp. Med. 210(5), 917–931 (2013). •• Demonstrates that in murine model, ILCs promote the development of colon cancer through producing IL-22, which induces Stat3 phosphorylation and proliferation.Crossref, Medline, CAS, Google Scholar
92. Bergmann H, Roth S, Pechloff K et al. Card9-dependent IL-1beta regulates IL-22 production from group 3 innate lymphoid cells and promotes colitis-associated cancer. Eur. J. Immunol. 47(8), 1342–1353 (2017).Crossref, Medline, CAS, Google Scholar
93. Chan IH, Jain R, Tessmer MS et al. Interleukin-23 is sufficient to induce rapid de novo gut tumorigenesis, independent of carcinogens, through activation of innate lymphoid cells. Mucosal Immunol. 7(4), 842–856 (2014).Crossref, Medline, CAS, Google Scholar
94. 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. 11(11), 1030–1038 (2010).Crossref, Medline, CAS, Google Scholar
95. Moskalenko M, Pan M, Fu Y et al. Requirement for innate immunity and CD90(+) NK1.1(-) lymphocytes to treat established melanoma with chemo-immunotherapy. Cancer Immunol. Res. 3(3), 296–304 (2015).Crossref, Medline, CAS, Google Scholar
96. Nussbaum K, Burkhard SH, Ohs I et al. Tissue microenvironment dictates the fate and tumor-suppressive function of type 3 ILCs. J. Exp. Med. 214(8), 2331–2347 (2017).Crossref, Medline, CAS, Google Scholar
97. Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328(5979), 749–752 (2010).Crossref, Medline, CAS, Google Scholar
98. Lewis JM, Burgler CD, Freudzon M et al. Langerhans cells facilitate UVB-induced epidermal carcinogenesis. J. Invest. Dermatol. 135(11), 2824–2833 (2015).Crossref, Medline, CAS, Google Scholar
99. Kim J, Kim W, Moon UJ et al. Intratumorally establishing type 2 innate lymphoid cells blocks tumor growth. J. Immunol. 196(5), 2410–2423 (2016).Crossref, Medline, CAS, Google Scholar
100. Irshad S, Flores-Borja F, Lawler K et al. RORgammat(+) innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Res. 77(5), 1083–1096 (2017). •• Shows the role of ILC3 in promoting lymphatic metastasis of breast cancer by modulating local chemokine milieu in tumor microenvironment through in vitro and in vivo experiments.Crossref, Medline, CAS, Google Scholar
101. Jovanovic IP, Pejnovic NN, Radosavljevic GD et al. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int. J. Cancer 134(7), 1669–1682 (2014).Crossref, Medline, CAS, Google Scholar
102. Wu Y, Yan Y, Su Z et al. Enhanced circulating ILC2s and MDSCs may contribute to ensure maintenance of Th2 predominant in patients with lung cancer. Mol. Med. Rep. 15(6), 4374–4381 (2017).Crossref, Medline, CAS, Google Scholar
103. Saranchova I, Han J, Zaman R et al. Type 2 innate lymphocytes actuate immunity against tumours and limit cancer metastasis. Sci. Rep. 8(1), 2924 (2018).Crossref, Medline, Google Scholar
104. Carrega P, Loiacono F, Di Carlo E et al. NCR(+)ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures. Nat. Commun. 6, 8280 (2015).Crossref, Medline, CAS, Google Scholar
105. Li J, Razumilava N, Gores GJ et al. Biliary repair and carcinogenesis are mediated by IL-33-dependent cholangiocyte proliferation. J. Clin. Invest. 124(7), 3241–3251 (2014).Crossref, Medline, CAS, Google Scholar
106. Crome SQ, Nguyen LT, Lopez-Verges S et al. A distinct innate lymphoid cell population regulates tumor-associated T cells. Nat. Med. 23(3), 368–375 (2017).Crossref, Medline, CAS, Google Scholar
107. Munneke JM, Bjorklund AT, Mjosberg JM et al. Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease. Blood 124(5), 812–821 (2014).Crossref, Medline, CAS, Google Scholar
108. Karrich JJ, Cupedo T. Group 3 innate lymphoid cells in tissue damage and graft-versus-host disease pathogenesis. Curr. Opin. Hematol. 23(4), 410–415 (2016).Crossref, Medline, CAS, Google Scholar
109. Hanash AM, Dudakov JA, Hua G et al. Interleukin-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft versus host disease. Immunity 37(2), 339–350 (2012).Crossref, Medline, CAS, Google Scholar

Vol. 11, No. 12

Metrics

Downloaded 246 times

History

Received 8 March 2018

Accepted 17 June 2019

Published online 26 June 2019

Published in print August 2019

Information

Keywords

Financial & competing interests disclosure

This study was funded by National Natural Science Foundation (grant numbers 81270598, 81473486 and 81770210); Key Research and Development Program of Shandong Province (grant number 2018CXGC1213); Technology Development Projects of Shandong Province (grant number 2017GSF18189); Taishan Scholar Foundation of Shandong Province; Shandong Provincial Engineering Research Center of Lymphoma; Key Laboratory for Kidney Regeneration of Shandong Province. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

PDF download