Myeloid derived suppressor cells (MDSCs) can induce the generation of Th17 response from naïve CD4+ T cells

Abstract

IL-17 producing CD4⁺ T cells (Th17) are identified as a subset of proinflammatory T cells present at the tumor site of various murine and human cancer cases and plays a crucial role in shaping the neoplastic process through fostering tumor angiogenesis and metastasis. However, the development of Th17 response in the tumor microenvironment has not yet been fully elucidated. Herein, we make an attempt to disclose the involvement of tumor infiltrating antigen presenting cells (APCs), especially tumor associated macrophages (TAMs) and myeloid derived suppressor cells (MDSCs) to polarize naïve CD4⁺ T cells toward IL-17⁺ T cells. We have found that MDSCs either isolated from the tumor site or generated in vitro are superior over TAMs to induce IL-17 production by naïve CD4⁺ T cells. Furthermore, we have shown that MDSCs mediated induction of IL-17⁺ T cell response is independent of MDSCs-T cell contact but crucially depends on the cytokines secreted by MDSCs. Our study will help to develop potential therapeutic strategies by harnessing the ability of MDSCs to induce IL-17 production by CD4⁺ T cells and thus restrict the generation of inflammatory Th17 population at the disease site.