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Overexpression and Immunosuppressive Functions of Transforming Growth Factor 1, Vascular Endothelial Growth Factor and Interleukin-10 in Epithelial Ovarian Cancer

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Author:: No author available

Journal Title:: Chinese Journal of Cancer Research

Issue:: 2

DOI:: 10.1007/sl1670-012-0130-V

Key Word:: Epithelial ovarian cancer;Tumor microenvironment;Immunosuppression;Cytokines

Abstract： Objective:Transforming growth factor-1 (TGF-β1),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).Methods:The expression levels of TGF-β1,VEGF and IL-10 in malignant tissue were evaluated by immunehistochemistry 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-β1,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.Results:TGF-β1,VEGF,and IL-10 were expressed in 100％,74.69％,and 54.96％ of EOC patients,respectively.TGF-β1 was an independent prognostic factor for EOC.IL-10 was significantly co-expressed with VEGF.In vitro,VEGF and TGF-β1 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-β1 and IL-10 induced Treg generation without antigen presentation in DCs.Conclusions:TGF-β1,VEGF and IL-10 play important roles in EOC and can lead to frequent immune evasion events.

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