IL-23 promotes the development of hepatocellular carcinoma through the induction of IL-17-producing ILC3 (TUM10P.1044)

Abstract

Abstract IL-23 has been shown to play a pathogenic role in autoimmunity through the promotion of Th17 cells. However, its role in tumor development remains controversial. Some studies demonstrated that IL-23 could activate T cells and NK cells to suppress tumor metastasis and growth. However, it has also been shown to promote tumor growth in colon cancer, lung cancer, breast cancer and melanoma. In the current study, we established a murine hepatocellular carcinoma (HCC) model and found that IL-23 could promote HCC development. The in vitro study demonstrated that IL-23 could directly promote HCC cell proliferation but not affect its apoptosis. Furthermore, although IL-23 could significantly increase the percent of Tc17 (CD8+IL-17+), the majority of IL-17-producing cells induced by IL-23 in the liver was innate lymphoid cell type 3 (ILC3). IL-17 could further suppress anti-tumor immune responses through the recruitment and promotion of myeloid derived suppressor cells (MDSC). Our study, for the first time, demonstrated that IL-23 could enhance HCC development through direct promotion of tumor cell proliferation, as well as suppressing anti-tumor immune response by inducing IL-17-producng ILC3.