乳腺癌异常表达B7-H4对T细胞分泌细胞因子和凋亡的影响  

B7-H4 expression in human breast carcinoma and its role on cytokine secretion and apoptosis of peripheral blood T cells

作　　者：沈依帆 黄文炼[1] 徐曼[1] 苏新良[2] 王欣[1] 汪涛[1] 

机构地区：[1]重庆医科大学基础医学院病理教研室,分子医学与肿瘤研究中心,重庆400016 [2]重庆医科大学附属第一医院内分泌乳腺外科,重庆400016

出　　处：《中国免疫学杂志》2016年第6期867-870,874,共5页Chinese Journal of Immunology

基　　金：重庆市自然科学基金(CSTC2009BB5268)项目

摘　　要：目的:探讨B7-H4在乳腺癌中的表达及其对外周血T细胞分泌细胞因子及增殖、凋亡的影响。方法:应用SP免疫组化法检测B7-H4在乳腺浸润性癌、癌旁组织和纤维腺瘤的表达。流式细胞术分析B7-H4对乳腺癌患者外周血活化T细胞增殖和凋亡的作用。ELISA芯片检测T细胞培养上清液细胞因子的含量。结果:B7-H4在乳腺浸润性癌的阳性表达率为84.62%(44/52),显著高于癌旁组织和纤维腺瘤组织(P<0.01,P<0.01)。体外淋巴细胞混合培养结果显示,与空白组比较,B7-H4对乳腺癌患者外周血活化T细胞的增殖指数Ki67无明显影响;但B7-H4诱导CD8^+T细胞凋亡的作用强于CD4^+T细胞。B7-H4组FOXP3^+T/CD4^+T也高于空白组(P<0.05)。B7-H4组较空白组细胞培养上清液中TGF-β1、IL-17含量均显著增高(P<0.05,P<0.05)。结论:乳腺浸润性癌异常表达B7-H4。B7-H4在体外能促进CD8^+T细胞凋亡、促进T细胞分泌TGF-β1和IL-17。B7-H4在削弱乳腺癌微环境的抗肿瘤细胞免疫中发挥一定作用。Objective：To explore B7-H4 expression in human invasive breast carcinomas and study the effect of recombinant human B7-H4 protein on the active peripheral blood T lymphocytes of the patients in vitro. Methods：B7-H4 expression was detected in 52 cases of breast cancer with immunohistochemistry staining. After the activated peripheral blood T lymphocytes of breast cancer patients were co-cultured with B7-H4, the proliferation, apoptosis and cell subtypes were tested by FCM, and the concentration of cytokines in the supernatant were detected by ELISA microarray. Results：B7-H4 was expressed in 84. 62% （44/52） of invasive breast cancers,with the positive rates significantly higher than that of fibroadenomas and the adjacent tissues of breast cancers（ P〈0. 01,P〈0. 01）. There were no significant differences of Ki67 positive rates of T cells between B7-H4 groups and blank groups;however,B7-H4 played stronger role in promoting apoptosis of CD8＋T cells than that of CD4＋T cells. The rate of FOXP3＋T/CD4＋T cells in B7-H4 groups were higher than that of blank groups （ P〈0. 05 ） . The concentration of TGF-β1 and IL-17 in the supernatant of B7-H4 co-cultured T cells were significantly higher than that of blank groups（P〈0. 05,P〈0. 05） . Conclusion：B7-H4 overexpresses in invasive breast carcinomas. In vitro,B7-H4 promotes apoptosis of CD8＋T cells,and the secretion of IL-17 and TGF-β1 by T cells . B7-H4 plays a role in weakening anti-tumor T cell immune response of the breast cancer microenviroment.

关 键 词：B7-H4 乳腺癌 CD8^+T细胞 细胞凋亡 TGF-Β1 IL-17 

分 类 号：R737.9[医药卫生—肿瘤]