Journal of Immunology Research / 2016 / Article / Fig 2

Review Article

Crosstalk between Innate Lymphoid Cells and Other Immune Cells in the Tumor Microenvironment

Figure 2

Anti- and protumor activities of group 2 innate lymphoid cells (ILC2). (a) The antitumor activity of ILC2 has been demonstrated in a model of lung metastatic melanoma. IL-33-activated ILC2 produce IL-5, which induces the recruitment and maintenance of eosinophils that display antitumorigenic activity. In contrast, ILC2 can also play an important role in tumor progression as shown in models of liver and breast cancer (b). A study in the 4T1 syngeneic model of breast cancer has shown that IL-33 produced by tumor cells is associated with the induction of a protumor environment characterized by increased numbers of MDSC and Treg. Contributing to the suppressive environment, an increased number of ILC2 secrete IL-5/IL-13 and target MDSC, which in turn secrete TGFβ (to activate and maintain Treg) and arginase (Arg) to inhibit natural killer (NK) cell activity. Under these immunosuppressive conditions, 4T1 tumors develop and metastasize. (c) Further, evidence of the dual role of ILC2 in tumor development has been highlighted by studies in models of liver cancer. Cell damage of epithelial cells lining the bile ducts (cholangiocytes) in the presence of IL-33-activated ILC2 leads to secretion of IL-13, which under normal conditions is used by epithelial cells to proliferate and induce tissue repair. However, under conditions of oncogenic priming (activation of protumor signaling pathways) the control of epithelial cells proliferation is lost and leads to tumor development.

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