Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer

Transforming growth factor-1 (TGF-beta 1), vascular endothelial growth factor (VEGF), and interleukin-10 (IL-10) may be critical cytokines in the microenvironment of a tumor, playing roles in immune suppression. This study was conducted to elucidate the roles and immunosuppressive functions of these cytokines in epithelial ovarian cancer (EOC). The expression levels of TGF-beta 1, VEGF and IL-10 in malignant tissue were evaluated by immune-histochemistry and compared with corresponding borderline, benign, and tumor-free tissues. Moreover, relationships among the levels of these cytokines and correlations between expression and the prognosis of EOC were analyzed by Pearson rank correlations and multi-factor Logistic regression. The roles of TGF-beta 1, VEGF, and IL-10 in the immunosuppressive microenvironment of ovarian cancer were studied through dendritic cell (DC) maturation and CD4+CD25+FoxP3+ Treg generation in vitro experiments. TGF-beta 1, VEGF, and IL-10 were expressed in 100%, 74.69%, and 54.96% of EOC patients, respectively. TGF-beta 1 was an independent prognostic factor for EOC. IL-10 was significantly co-expressed with VEGF. In vitro, VEGF and TGF-beta 1 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-10 that accumulated around the tumor site. TGF-beta 1 and IL-10 induced Treg generation without antigen presentation in DCs. TGF-beta 1, VEGF and IL-10 play important roles in EOC and can lead to frequent immune evasion events.OncologySCI(E)PubMed中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)13ARTICLE2130-1372