Transcription factor c-Maf drives anti-tumor Th17 responses by enhancing CD8+ T cell cytotoxicity 3465

Abstract Description CD4 T cells play anti or pro-tumor role in tumor immunity, and their transcriptional mechanisms underlying these opposing roles remain understood. Transcription factor c-Maf regulates cytokine production across various CD4 T cell subsets. To investigate the role of c-Maf in CD4 T cells within tumor immunity, we generated specifically c-Maf-deficient CD4 T cells (CD4T dc-Maf) mice and these mice exhibited increased tumor volume of both B16 and MC38 tumor, as well as higher tumor burdens in colitis associated colon cancer (CAC) induced by AOM/DSS treatment, compared to littermate controls. These results indicate that c-Maf in CD4 T cells plays an anti-tumor role. Notably, a reduction in Tbet+IFNγ+ Th1 cells, RORγt+IL-17A+ Th17 cells were observed within both tumor-infiltrating lymphocytes (TILs) from MC38 tumor-implanted mice and lamina propria lymphocytes (LPLs) from CAC models. Additionally, although CD8 T cells expressed similar levels of c-Maf in both groups, CD8 T cells from CD4T dc-Maf mice exhibited significantly reduced expression of cytotoxic markers, including CD107a, granzyme B, and IFNγ, compared to littermate controls. We also transferred OT-II+Th1 or OT-II+Th17 cells into MC38-OVA tumor-bearing mice, and found that Th17 cells from CD4T dc-Maf mice exhibited reduced tumor volume compared to controls, while no differences in the transfer of Th1 cells. These findings underscore c-Maf in Th17 cell-mediated anti-tumor responses through activation of CD8 T cells. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)