IL-10 INDUCES MACROPHAGE IMMUNOSUPPRESSION BY UPREGULATING TRANSCRIPTION FACTOR C-MAF

Interactions between tumor cells and immune cells play critical roles in tumor initiation, progression, and metastasis. Indeed, tumor-derived supernatant contains suppressive factors contributing to tumor growth and evasion of immune cells. It is important, therefore, to examine them and their effects on immune cells in order to aid in the development of new approaches to combat tumor growth. Herein, we demonstrated that the presence of tumor-derived supernatant significantly enhanced the induction of transcription factor c-maf in peritoneal macrophages, and also converted them to immunosuppressive M2-like macrophages. Subsequently, we examined the different components of the tumor-derived supernatant and their effects on c-maf expression; thus, we tested three known factors: lactic acid, citric acid, and interleukin-10 cytokine. Through experimentation, we ascertained that both lactic and citric acid had no effect on c-maf expression; however, interleukin-10 was required for the expression of c-maf in peritoneal macrophages, since the blocking of the IL-10 resulted in abrogation of c-maf expression induced by tumor-derived supernatant. That correlates with the acquisition of peritoneal macrophages of an M2-like phenotype that can suppress the proliferation of antigen-specific CD8+ T cells but not IFN-γ production. Overall, this study emphasized the importance of exploring the various components of tumor-derived supernatant, and how they regulate immune cell functions.