TTTTWe have been studying the function of group 2 innate lymphoid cells 33NKM1MDSCILC3ILC2EosinophilILC1ILC2M2ImmunogenicPoorly ImmunogenicElimination (Innate and adaptive immunity)Equilibrium or dormancy (Adaptive immunity)Escape (Tumor growth and metastasis)(ILC2) capable of producing large amounts of type 2 cytokines, such as IL-4, IL-5 and IL-13. Although ILC2s are rare in secondary lymphoid or-gans relative to other immune cells, they harbor a unique location within non-lymphoid tissues, especially skin, mucosal barriers and adipose tissues. Despite intensive studies on the role of ILC2 in allergic disorders, their role in anti-tumor immunity has been obscure and controversial. Cancer immunoediting comprises three phases: elimination (immunosurveillance by immune cells), equilibrium (preventing tumor outgrowth and sculpting tumor immunogenic-ity by adaptive immune cells) and escape (expression of suppressing ligand such as PD-L1 by tumor cells and recruitment of immunosuppressive cells). The study of ILCs in cancer is still in its infancy. Indeed, ILCs have been sepa-rately associated with tumor-promoting as well as tumor-suppressing activities and involvement of ILCs in cancer immunoediting has been obscure. We have shown that ILC2s play a tumor-suppressing role in a mouse melanoma system. In humans, expression of IL33 (activation of ILC2) and SIGLEC8 (recruitment of eosinophils) are associated with better overall survival in melanoma patients, whereas no correlation was observed between the expression levels of IL33 and SIGLEC8 and overall survival for some other tumors, such as lung squamous cell carcinoma and pancreatic adenocarcinoma. Among ILCs, NK cells are well known for their antiviral and antitumor activities. ILC1s produce IFN-γ, which induces proinflammatory M1 macrophages. ILC2s recruit and activate eosino-phils through the release of IL-5, which displays suppressing activity for tumors such as melanoma. On the other hand, ILC2s induce anti-inflammatory M2 macrophages. The presence of ILC3s correlates with the density of tertiary lym-phoid structures that are associated with favorable prognosis in some tumors such as non-small cell lung carcinoma. A more comprehensive understanding of how these mechanisms develop will be crucial in harnessing the power of immunotherapy to treat a variety of tumors.Figure: Concept of cancer immunoediting by innate lymphoid cells (ILCs)Cancer immunoediting is composed of three phases: elimination, equilibrium, and escape. In the elimination phase, ILCs alone or in combination with several differ-ent components of the innate and adaptive immune system may protect the host from tumor formation. However, if this process is not successful, tumor cells may enter the equilibrium phase, in which they may be either maintained chronically or immunologically sculpted by the components of the adaptive immunity to produce new populations of tumor variants. These variants may eventually acquire the ability to circumvent recognition and destruction by ILCs through a variety of mechanisms and become clinically detectable during the escape phase. Abbreviations: M1, pro-inflammatory M1 macrophages; M2 anti-inflammatory M2 macro-phages; MDSC, myeloid-derived suppressor cells.Recent Major PublicationsWagner M, Koyasu S. Innate lymphoid cells in skin ho-meostasis and malignancy. Front Immunol 12, 758522 (2021)Ishihama H, Ishii K, Nagai S, Kakinuma H, Sasaki A, Yo-shioka K, Kuramoto T, Shiono Y, Funao H, Isogai N, Tsuji T, Okada Y, Koyasu S, Toyama Y, Nakamura M, Aizawa M, Matsumoto M. An antibacterial coated polymer prevents biofilm formation and implant-associated infection. Sci Rep 11, 3602 (2021)Sumiyoshi M, Kotani Y, Ikuta Y, Suzue K, Ozawa M, Katakai T, Yamada T, Abe T, Bando K, Koyasu S, Kanaho Y, Watanabe T, Matsuda S. Arf1 and Arf6 synergistically maintain survival of T cells during activation. J Immu-nol 206, 366-375 (2021)Laboratory for Immune Cell SystemsTeam Leader: Shigeo Koyasu
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