Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas
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Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas
Journal of Chongqing Medical UniversityVol. 37, Issue 10, Pages: 859-863(2012)
作者机构:
1. 重庆医科大学1. 基础医学院病理学教研室、分子与肿瘤研究中心
2. 附属第一医院妇产科,重庆,400016
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Published:2012,
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CHEN Yu, XU Man, XIAO Lin, et al. Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas. [J]. Journal of Chongqing Medical University 37(10):859-863(2012)
DOI:
CHEN Yu, XU Man, XIAO Lin, et al. Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas. [J]. Journal of Chongqing Medical University 37(10):859-863(2012)DOI:
Promotion of apoptosis of CD4+ T and CD8+ T lymphocytes induced by aberrant expression of programmed death ligand-1 in human cervical carcinomas
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。
Abstract
Objective:To investigate the expression of programmed death ligand-1(PD-L1) in human cervical carcinoma and the association between PD-L1 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-L1 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 infil-trating CD4+ T and CD8+ T lymphocytes was determined by immunofluorescent staining and the apoptotic promoting effect of recombi-nant 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. Con-clusions:PD-L1 is aberrantly expressed in cervical cancer. The expression of PD-L1 associates with lymphocytic apoptosis and de-crease of tumor infiltrating CD8+ T cells. PD-L1 promotes apoptosis of activated CD4+ T and CD8+ T cells by PD-L1/PD-1 pathway.
关键词
子宫颈癌程序性死亡配体-1程序生死亡受体-1T淋巴细胞凋亡
Keywords
cervical cancerprogrammed death ligand-1programmed death receptor-1T lymphocytesapoptosis