Ambiguous roles of innate lymphoid cells in chronic development of liver diseases

Figure 4 Possible innate lymphoid cell interactions in liver tumor immunity. ILC1s have both antitumor and protumor effects according to the properties of cytokines secreted. IFN-γ and TNF-α have antiproliferative, antiangiogenic and proapoptotic effects against cancer cells. In addition to promoting the polarization of CD4⁺ T cells into Th1 cells, they can also boost the responses of macrophages, NK cells and CTLs, leading to a strong antitumor response. On the contrary, their ambiguous roles enable them to enhance tumor formation, growth and spread. ILC2s may contribute to tumor progression either directly through the tumorigenic effects of IL-13, or indirectly by stimulating M2 macrophages and MDSCs through IL-13. The production of amphiregulin suggests that ILC2s may further inhibit antitumor immune responses either directly or via stimulation of Tregs. IL-33 could also induce the secretion of a massive amount of CXCR2 ligands from ILC2s as well as create a tumor microenvironment wherein tumor cells express CXCR2, leading to apoptosis of active tumor cells. ILC3s might promote antitumor responses by enhancing leukocyte invasion, promoting TLSs’ induction and through the antitumor effects of IL-17 and IL-22. Conversely, ILC3s may promote tumor formation and progression by IL-17 and IL-22 as well according to the phase of responses and specific tumor microenvironment. CTL: Cytotoxic T lymphocyte; IL: Interleukin; ILC: Innate lymphoid cell; IFN: Interferon; MDSC: Myeloid-derived suppressor cell; NK: Natural killer; Th: T helper; TLS: Tertiary lymphoid structure; TNF: Tumor necrosis factor; Tregs: T regulatory cells.