Interleukin (IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer

•Administration of IL-24 increased the number of IFN-γ-producing CD8+T cell and especially enhanced the cytotoxicity of CD8+T cells.•The number and activity of CD8+T cells in TILs were increased, while the number of Treg cells in TILs was decreased greatly by IL-24.•The anti-tumor effect of IL-24 as an immunological regulatory molecule was dependent on CD8+T cells and not CD4+ T cells.•IL-24 promoted IFN-γ production via the CD8+ T cells and that IL-24 expression correlated inversely with metastasis and clinical tumor stages. Interleukin-24 (IL-24) is a novel tumor suppressor and can mediate the induction of Th1-type cytokines from peripheral blood mononuclear cells. The individual properties of IL-24 have been previously examined; however, its in vivo immunological consequences and antitumor properties have not been previously evaluated with respect to colon cancer, the most commonly diagnosed cancer in China. Thus, we evaluated whether IL-24 could inhibit the progression of colon cancer in murine models with intact immune competence and explored the mechanisms underlying the immunological effects of IL-24 on colon cancer progression in vivo. In these murine models, we found that IL-24 promoted CD4+ T cells and CD8+ T cells to secrete interferon gamma and enhanced the cytotoxicity of CD8+ T cells in vivo. More importantly, we demonstrated that IL-24 transformed the tumor microenvironment and enhanced antitumor effects in favor of tumor eradication. Additionally, IL-24 expression correlated inversely with the clinical stage of human colorectal cancer. Thus, our study establishes a role of IL-24 in promoting antitumor immune responses and supports the development of a novel cytokine immunotherapy against colon cancer.