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

作　　者：Chan-zhen Liu Li Zhang Xiao-hong Chang Ye-xia Cheng Hong-yan Cheng Xue Ye Tian-yun Fu Jun Chen Heng Cui 

机构地区：[1]Gynecology Oncology Center,Peking University People's Hospital,Beijing 100044,China

出　　处：《Chinese Journal of Cancer Research》2012年第2期130-137,共8页中国癌症研究（英文版）

基　　金：supported by the Natural Science Foundation of China(No.30872750);the Natural Science Foundation of Beijing(No.7092108)

摘　　要：Objective： Transforming growth factor-1 （TGF-βI）, vascular endothelial growth factor （VEGF）, and interleukin-lO （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 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-βI, VEGF, and IL-lO 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-IO were expressed TGF-β1 was an independent prognostic factor for EOC n 100%, 74.69%, and 54.96% of EOC patients, respectively. L-IO was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β31 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-IO that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs. Conclusions： TGF-βI, VEGF and IL-IO play important roles in EOC and can lead to frequent immune evasion events.Objective： Transforming growth factor-1 （TGF-βI）, vascular endothelial growth factor （VEGF）, and interleukin-lO （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 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-βI, VEGF, and IL-lO 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-IO were expressed TGF-β1 was an independent prognostic factor for EOC n 100%, 74.69%, and 54.96% of EOC patients, respectively. L-IO was significantly co-expressed with VEGF. In vitro, VEGF and TGF-β31 strongly interfered with DC maturation and consequently led to immature DCs, which secreted high levels of IL-IO that accumulated around the tumor site. TGF-β1 and IL-10 induced Treg generation without antigen presentation in DCs. Conclusions： TGF-βI, VEGF and IL-IO play important roles in EOC and can lead to frequent immune evasion events.

关 键 词：Epithelial ovarian cancer Tumor microenvironment IMMUNOSUPPRESSION CYTOKINES 

分 类 号：Q78[生物学—分子生物学] Q463