【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。更多还原

【Abstract】 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-L2group and PD-L2+anti-PD-1 group respectively.After these active T cells were cultured 72h,their apoptotic rates were detected by flow cytometry.Results PD-L2expressed in 53.3%(32/60)cervical squamous cell carcinomas,and it′s expression associated with lymph node metastasis of these cases(P<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 expresses 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.更多还原