人子宫颈癌异常表达程序性死亡配体-1并促CD4＋T和CD8＋T细胞凋亡  

Promotion of apoptosis of CD_4^+ T and CD_8^+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas

作　　者：陈瑜[1] 徐曼[1] 肖琳[2] 耿卫朴[1] 王婷婷[1] 黄文炼[1] 

机构地区：[1]重庆医科大学基础医学院病理学教研室、分子与肿瘤研究中心,重庆400016 [2]重庆医科大学附属第一医院妇产科,重庆400016

出　　处：《重庆医科大学学报》2012年第10期859-863,共5页Journal of Chongqing Medical University

基　　金：重庆市自然科学基金资助项目(编号:CSTC2009BB5268)

摘　　要：目的:探讨程序性死亡配体-1(Programmed death ligand-1,PD-L1)在人子宫颈癌的表达及其与肿瘤内CD4+T和CD8+T细胞浸润的相关性,体外实验观察重组人PD-L1蛋白对宫颈癌患者外周血T细胞凋亡的影响。方法:采用免疫组化SP法检测PD-L1在10例正常人宫颈组织和67例宫颈癌组织中的表达以及死亡受体-1(Programmed death receptor-1,PD-1)在宫颈癌内浸润淋巴细胞的表达;TUNEL法检测肿瘤内浸润的淋巴细胞凋亡;免疫荧光分析宫颈癌内浸润的CD4+T和CD8+T淋巴细胞数量;流式细胞术分析PD-L1促进宫颈癌患者外周血活化CD4+T和CD8+T细胞凋亡情况。结果:正常子宫颈上皮不表达PD-L1;宫颈癌PD-L1的表达率为70%(47/67)。部分宫颈癌内浸润的淋巴细胞表达PD-1,且淋巴细胞存在凋亡现象。PD-L1阳性宫颈癌肿瘤内浸润的CD8+T细胞数量明显减少(P<0.05)。体外实验发现PD-L1与健康人或宫颈癌患者外周血活化T细胞混合培养48 h后,T细胞凋亡率明显高于空白组,2组平均凋亡率分别为(32.8±1.4)%、(38.3±1.5)%(P<0.05)和(27.7±1.3)%、(30.9±1.9)%(P<0.05);抗PD-1抗体使PD-L1诱导的T细胞凋亡率下降,分别为(29.8±1.6)%和(31.6±1.4)%(P>0.05)。PD-L1对人外周血活化CD4+T和CD8+T细胞均有促凋亡作用。结论:人子宫颈癌异常表达PD-L1与肿瘤内浸润的淋巴细胞凋亡及CD8+T细胞数量减少有关。PD-L1经PD-1促进活化的CD4+T和CD8+T细胞凋亡。Objective：To investigate the expression of programmed death ligand-1 （PD-L1） in human cervical carcinoma and the association between PD-LI expression and T cell infiltration and to observe the effect of PD-L1 on apoptosis of active peripheral blood T lymphocytes of patients with cervical cancer in vitro. Methods：PD-Ll and programmed death receptor-1 （PD-1） in human cervical carcinoma expressions were determined in 10 cases of normal cervical tissues and 67 cases of cervical carcinoma tissues by immunohistochemistry staining;the apoptosis of tumor infiltrating lymphocytes was examined by TUNEL assay;the number of tumor infiltrating CD4＋ T and CDs＋ T lymphocytes was determined by immunofluorescent staining and the apoptotic promoting effect of recombinant human PD-L1 protein on peripheral blood CD4＋T and CD8＋T lymphocytes was analyzed by flow cytometry. Results：No expression of PD-L1 in normal cervical epithelium was observed but expression of PD-L1 was found in 70% （47/67）cervical cancer tissues. PD-1 expression was found in part of tumor infiltrating lymphocytes. Some tumor infiltrating lymphocytes showed apoptosis. The tumor infiltrating CD8＋T cells were significantly reduced in PD-L1 positive cervical carcinoma cases（P〈0.05）. In vitro,recombinant hu- man PD-L1 induced apoptosis of activated peripheral blood T lymphocytes of healthy people and cervical cancer patients and the T cell apoptotic rates were significantly higher than those in blank group,which were （32.8 ± 1.4）%, （38.3 ± 1.5）%（P〈0.05） and （27.7 ± 1.3）%, （30.9 ± 1.9）%（P〈0.05） respectively. Anti-PD-1 antibody depressed PD-L1 induced T cells apoptosis,the apoptotic rates were （29.8 ± 1.6）% and （31.6 ± 1.4）%（P〉0.05）. PD-L1 induced apoptosis of peripheral blood CD8＋T and CD4＋T cells. Conclusions：PD-Ll is aberrantly expressed in cervical cancer. The expression of PD-L1 associates with lymphocytic apoptosis and decrease of tumor infiltrating CD8＋T cells. PD-L1 promotes

关 键 词：子宫颈癌 程序性死亡配体-1 程序生死亡受体-1 T淋巴细胞 凋亡 

分 类 号：R392.3[医药卫生—免疫学] R392.11[医药卫生—基础医学]