Obesity Promotes Tumor Immune Evasion in Ovarian Cancer Through Increased Production of Myeloid-Derived Suppressor Cells via IL-6

Abstract

Background Obesity is defined as a chronic, low-grade inflammatory disease that can cause obesity-associated disorders, such as cancer. Obesity has traditionally been thought to be a risk factor for ovarian cancer. Few reports have focused on the specific pathogenesis of obesity-related ovarian cancer. When considering the correlation between obesity and the relative risk of death from ovarian cancer, we investigated whether obesity promotes tumor immune escape in ovarian cancer. Results In the present study, obese mice were found to have higher rates of tumor growth and tumor infiltration than mice of normal weight. Obesity increased the proportion of myeloid-derived suppressor cells (MDSCs) in peripheral blood compared with mice of normal weight. In addition, the levels of CCL25, CD40L, GM-CSF, IL-5, IGFBP2, IL-6, MMP3, and MMP9 in the peripheral blood, bone marrow, and ovarian tissue of obese mice were higher than in mice of normal weight. Moreover, IL-5 and IL-6 significantly enhanced the expression levels of S100A8 and S100A9 in MDSCs. When compared with the levels in mice of normal weight, the expression levels of S100A8 and S100A9 in the MDSCs of OB/OB mice were also higher within the tumor microenvironment. The infiltration of MDSCs in ovarian cancer was found to be positively correlated with the expression levels of IL-6. The IL-6 expression levels in ovarian cancer tissue are positively correlated with the expression levels of S100A8 and S100A9, which is consistent with the results of previous animal experiments. Finally, we found that LMT28 can suppress the tumor growth by inhibiting IL-6. Conclusion Obesity promotes the expression of the MDSC-related immunosuppressive genes S100A8 and S100A9 by upregulating IL-6, thus promoting tumor immune evasion and metastasis in ovarian cancer.