PD-L1在人胶质瘤中的表达及其对肿瘤内浸润性T细胞凋亡的影响

目的 探讨程序性死亡-配体1(PD-L1)在人胶质瘤组织中的表达及其对肿瘤内浸润性T细胞凋亡的影响.方法 对2007-2011年解放军第101医院收治的80例胶质瘤患者肿瘤组织及18例正常脑组织进行PD-L1免疫组织化学方法检测,同时检测程序性死亡受体-1(PD-1)在胶质瘤浸润性T淋巴细胞的表达,进行相关性分析,TUNEL法检测胶质瘤内浸润性淋巴细胞的凋亡,应用流式细胞术分析PD-L1促进胶质瘤患者外周血中活化T细胞的凋亡情况.结果 正常脑组织不表达PD-L1,PD-L1在胶质瘤中的阳性表达率为42.50％(34/80),与胶质瘤病理分级、坏死和预后相关(P＜0.05).部分胶质瘤组织及浸润T淋巴细胞表达PD-1,且PD-L1阳性的胶质瘤病例淋巴细胞凋亡表达较PD-L1阴性病例明显增高.PD-L1组患者外周血活化T细胞的凋亡率为42.55％明显高于空白对照组,加入抗PD-1阻断PD-L1与T淋巴细胞结合后,PD-L1+抗PD-1组活化T淋巴细胞凋亡率下降到26.80％.结论 人胶质瘤异常高表达PD-L1并与PD-1结合促进淋巴细胞的凋亡.

Expression of programmed death ligand-1 in human glioma and its influence to intratumor infiltrating T lymphocyte apoptosis

Objective To investigate the expression of programmed death ligand-1(PD-L1) in glioma and its influence to intratumor infiltrating T lymphocyte apoptosis.Methods PD-L1 in 18 cases of normal brain tissues and 80 cases of glioma tissues treated in this hospital during 2007 to 2011 was determined by immunohistochemistry staining,meanwhile the PD-L1 expression in glioma infiltrating T lymphocyte was determined.The correlation analysis was performed.The apoptosis of intratumor infiltrating lymphocytes was examined by TUNEL assay;the peripheral blood activated T lymphocyte apoptosis promoted by PD-L1 was analyzed by flow cytometry.Results No expression of PD-L1 in normal brain tissues was observed,but the positive expression rate in glioma was 42.50 ％ (34/80),which was correlated with pathological grade,necrosis and prognosis(P＜0.05).PD-1 was expressed in part of tumor infiltrating T lymphocytes and glioma tissues,moreover the lymphocyte apoptosis expression in the cases of PD-L1 positive glioma was significantly increased compared with that in the cases of PD-L1 negative glioma.The apoptosis rate of activated T lymphocytes was 42.55 ％ respectively,which was significantly higher than that in the blank group;however,adding anti-PD-1 for blocking the combining of PD-L1 with T lymphocyte,the lymphocytes apoptotic rate in the PD-L1+ anti-PD-1 group was dropped to 26.80％.Conclusion PD-L1has aberrantly high expression in human glioma and is combined with PD-1 to promote the apoptosis of lymphocyte.