Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer
Overexpression and immunosuppressive functions of transforming growth factor 1, vascular endothelial growth factor and interleukin-10 in epithelial ovarian cancer
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DOI：
10.1007/s11670-012-0130-y
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发表时间：
2012-06-01
影响因子：
5.1
通讯作者：
Cui, Heng
中科院分区：
文献类型：
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作者：
Liu, Chan-zhen;Zhang, Li;Cui, Heng
转化生长因子-1(TGF-β1)、血管内皮生长因子(VEGF)和白介素10(IL-10)可能是肿瘤微环境中的重要细胞因子，发挥免疫抑制作用。为探讨这些细胞因子在卵巢上皮性癌(EOC)中的作用和免疫抑制作用，采用免疫组织化学方法检测了恶性卵巢癌组织中转化生长因子-β1、血管内皮生长因子和IL-10的表达水平，并与相应的交界性、良性和无肿瘤组织进行了比较。采用皮尔逊等级相关分析和多因素Logistic回归分析这些细胞因子水平之间的关系以及表达与卵巢癌预后的关系。通过体外树突状细胞(DC)成熟和CD4+CD25+FoxP3+Treg生成实验，研究了转化生长因子-β1、血管内皮生长因子和IL-10在卵巢癌免疫抑制微环境中的作用。卵巢癌患者中，转化生长因子-β1、血管内皮生长因子和IL-10的表达分别为100%、74.69%和54.96%。转化生长因子-β1是卵巢癌的独立预后因素。IL-10与血管内皮细胞生长因子显著共表达。在体外，血管内皮生长因子和转化生长因子-β1强烈干扰DC的成熟，从而导致未成熟的DC分泌高水平的IL-10，并聚集在肿瘤部位。转化生长因子-β1和白介素10诱导树突状细胞在无抗原提呈的情况下产生Treg，转化生长因子-β1、血管内皮生长因子和白介素10在卵巢上皮性癌中起重要作用，可导致频繁的免疫逃避事件。
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.