PD-L2在宫颈鳞状细胞癌的表达及对外周血T细胞凋亡的影响  

The expression of PD-L2 in human cervical carcinomas and the influence to peripheral blood T lymphocytes apoptosis

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

机构地区：[1]重庆医科大学病理教研室/分子与肿瘤研究中心,400016

出　　处：《重庆医学》2014年第9期1052-1054,1057,共4页Chongqing medicine

基　　金：重庆市自然科学基金资助项目(CSTC2009BB5268)

摘　　要：目的检测负性共刺激分子PD-L2在人宫颈鳞状细胞癌的表达情况,分析其与患者临床病理特征的相关性,并观察重组人PD-L2蛋白对患者外周血T细胞凋亡的影响。方法采用免疫组织化学染色检测PD-L2蛋白在60例宫颈鳞状细胞癌患者癌组织中的表达,并统计分析PD-L2蛋白表达与宫颈鳞状细胞癌患者临床病理特征的相关性。将患者外周血T淋巴细胞分为空白对照组、PD-L2组和PD-L2+抗PD-1组单克隆抗体组,流式细胞术分析各组T细胞的凋亡率。结果宫颈鳞状细胞癌表达PD-L2的阳性率为53.3%(32/60)。PD-L2的表达与宫颈鳞状细胞癌的淋巴结转移相关(P<0.05)。PD-L2组宫颈鳞状细胞癌患者外周血活化CD4+T和CD8+T的凋亡率分别为17.0%和22.4%,明显高于空白对照组9.0%和16.2%;加入抗PD-1阻断PD-L2与T淋巴细胞、PD-1结合后,PD-L2+抗PD-1组CD4+T和CD8+T淋巴细胞凋亡率下降到11.1%和17.5%。结论宫颈鳞状细胞癌细胞异常表达PD-L2,且与肿瘤的淋巴结转移有关。PD-L2通过促进T细胞凋亡而削弱宫颈微环境的抗肿瘤免疫,并促进肿瘤的淋巴结转移。PD-L2/PD-1途径有可能成为宫颈鳞状细胞癌免疫治疗的靶点之一。Objective To determine PD-L2 expression in human cervical squamous cell carcinomas and analyze its association with the clinical and pathologic characteristics of these cases ;observe the role of recombinant PD-L2 protein on apoptosis of active peripheral blood T lymphocytes of cervical carcinoma patients .Methods PD-L2 expression in cervical squamous cell carcinomas was determined by immunohistochemistry staining ,and the association between PD-L2 expression with the clinical and pathologic characteristics of these cases was analyzed .In vitro ,the peripheral blood T lymphocytes of cervical carcinoma patients were divided into blank group ,PD-L2 group and PD-L2＋anti-PD-1 group respectively .After these active T cells were cultured 72 h ,their apop-totic rates were detected by flow cytometry .Results PD-L2 expressed in 53 .3% （32/60）cervical squamous cell carcinomas ,and it′s expression associated with lymph node metastasis of these cases （P＆lt; 0 .05） .In vitro ,PD-L2 promoted apoptosis of CD4＋ T and CD8＋ T lymphocytes ,the apoptotic rates were 17 .0% and 22 .4% respectively ,which were higher than 9 .0% and 16 .2% of blank group;however ,the apoptotic rates dropped to 11 .1% and 17 .5% in PD-L2＋anti-PD-1 group .Conclusion PD-L2 aberrantly ex-presses in cervical squamous cell carcinomas and is associated with their lymph node metastasis .PD-L2 promotes apoptosis of T lymphocytes and depresses the anti-tumor immunity of cervical microenvironment ,and promotes lymph node metastasis of these cancers .PD-L2/PD-1 pathway may be a potential immunotherapy target of cervical squamous cell carcinomas .

关 键 词：宫颈肿瘤 T淋巴细胞 淋巴转移 PD-L2 

分 类 号：R737.33[医药卫生—肿瘤]