Interaction Between Treg Cells and Tumor-associated Macrophages in the Tumor Microenvironment of Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Inflammatory cells in the EOC microenvironment play a key role in tumor progression. In the present study, we investigated the mechanism of the accumulation of regulatory T cells (Tregs) induced by interleukin-10 (IL-10) derived from tumor-associated macrophages (TAMs) in the EOC microenvironment. The frequency of Tregs and TAMs was detected by immunofluorescence in 40 EOC tissues and 20 benign ovarian tumors, as well as the expression of IL-10 which was assessed by immunohistochemistry. It was found that the frequency of Treg cells and TAMs was significantly higher in the EOC than those in the benign ovarian tumors. The expression of IL-10 was also found to be higher in the EOC than that in the benign tumors. EOC patients with a high frequency of Tregs exhibited a significantly shorter overall survival time compared to those with a low frequency of Tregs. In addition, the expression of IL-10 in ascites and blood serum and the IL-10 released in the co-cultured system supernatants were detected by ELISA. Following CD4+ T-cell co-culturing with macrophages and IL-10, it was observed by flow cytometric analysis that the frequency of Treg cells was increased in the presence of IL-10. It was also established that IL-10 released in the co-cultured supernatants was increased. We also detected the mechanism of Treg cells induced by IL-10 in vivo. The SKOV3 cell tumor volume and weight were much higher in the presence of IL-10 in a mouse subcutaneous model. These data suggest that IL-10 secreted by TAMs increase the frequency of Treg cells through the activation of Foxp3 during T-cell differentiation and promotes tumor progression.