Interleukin (IL)-24 transforms the tumor microenvironment and induces anticancer immunity in a murine model of colon cancer. (July 2016)

• Record Type: Journal Article
• Authors: Ma, Yun-Feng; Ren, Yi; Wu, Cai-Jun; Zhao, Xiao-Hui; Xu, Hua; Wu, Da-Zhou; Xu, Jiru; Zhang, Xiao-Lian; Ji, Yanhong
• Is Part Of: Molecular immunology. Volume 75(2016:Jul.)
• Page Start: 11
• Page End: 20
• Publication Date: 2016-07
• Subjects: IL-24 interleukin-24 -- PBMCs peripheral blood mononuclear cells -- MDA melanoma differentiation-associated gene -- IFN-γ interferon-α -- CTLA4 cytotoxic T-lymphocyte-associated protein 4 -- PD1 programmed cell death 1 -- TILs tumor infiltrating lymphocytes; Interleukin-24 -- T cells -- Immunotherapy -- Cytokine -- Tumor microenvironment; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2016.05.010
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: 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. Abstract: 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.