IL‐33 inhibits the differentiation and immunosuppressive activity of granulocytic myeloid‐derived suppressor cells in tumor‐bearing mice

Myeloid‐derived suppressor cells (MDSCs) contribute to tumor‐mediated immune escape by suppressing antitumor immune responses. Interleukin‐33 (IL‐33) is capable of regulating various immune cell populations; however, the effects of IL‐33 on the differentiation of MDSCs have not been well characterized. In this study, we evaluated the effects of IL‐33 on MDSCs and found that IL‐33 significantly reduced the differentiation of lineage‐negative bone marrow progenitor cells into granulocytic MDSCs (G‐MDSCs). IL‐33‐treated MDSCs exhibited diminished immunosuppressive capacity; reduced inhibition on T‐cell proliferation and interferon‐γ production, and diminished production of reactive oxygen species. However, IL‐33 treatment did not affect the frequency of monocytic MDSCs (M‐MDSCs) or their production of nitric oxide and expression of arginase‐1. Additionally, compared with control MDSCs, IL‐33‐treated MDSCs had reduced capacity to induce the differentiation or expansion of Treg cells. Moreover, in vivo IL‐33 administration significantly decreased MDSCs and G‐MDSCs accumulation in the spleen and tumor microenvironment. Also, despite increasing CD4 + and CD8 + T‐cell infiltration, IL‐33 administration markedly decreased Treg‐cell population in tumor microenvironment. Taken together, our findings indicate that IL‐33 reduces the frequency and immunosuppressive activity of G‐MDSCs and ultimately the extent of tumor growth.