PD-L1在人子宫颈癌细胞异常表达并促T细胞凋亡

目的 探讨人子宫颈癌中负性协同刺激分子PD-L1的表达和它与肿瘤浸润淋巴细胞的关系以及PD-L1融合蛋白促宫颈癌患者外周血活化T细胞凋亡的作用.方法 采用免疫组化S-P法检测67例宫颈癌组织及20例正常宫颈组织中PD-L1的表达,分析PD-L1同临床病理特征的相关性,免疫荧光观察肿瘤浸润淋巴细胞数量,TUNEL法检测T细胞凋亡,体外实验将PD-L1融合蛋白细胞加入PHA刺激活化的宫颈癌患者外周血T细胞中共同培养,流式细胞术分析T细胞凋亡率和CD8+/CD4+T细胞比例.结论 正常子宫颈组织不表达PD-L1；宫颈癌组织中PD-L1的表达率为70％.宫颈癌PD-L1的表达与宫颈癌浸润深度相关(P＜0.05).PD-L1阳性病例肿瘤局部浸润淋巴细胞存在凋亡且CD8+T细胞数量明显减少；PD-L1融合蛋白组T细胞凋亡率明显高于抗PD-1组和空白对照组T细胞,分别为32.7％、18.3％和17.9％；CD8+T/CD4+T细胞的比值低于加入抗PD-1组和空白对照组,分别为0.864、0.894和0 907.结论 PD-L1在子宫颈癌中高表达且与肿瘤浸润程度及肿瘤浸润淋巴细胞数量减少有关,PD-L1能促进活化的T细胞尤其是CD8+T细胞的凋亡.

Abnormal Expression of PD-L1 and Its Role of Promoting Apoptosis of T Cells in Human Cervical Carcinomas

Objective To investigate the expression of co-stimulatory molecule PD-L1 and the association between PD-L1 expression and T cell infiltration in human cervical carcinomas; and its role of promoting apoptosis of active＇peripheral blood T lymphooytes of cervical cancer patients in vitro. Methods PD-L1 and PD-1 expression was respectively determined in twenty cases of normal cervical tissue and 67 cases of cer- vical carcinomas by immunohistoehemistry staining;the relationship of PD-L1 expressions to clinical and pathologic characteristics was evalu- ated ; the tumor infiltrating T ceils were determined by immunofluorescent staining; and the apoptosis of tumor infiltrating lymphocytes was ex- amined by TUNEL assay in those eases;Human PD-L1-Ig,human PD-L1-Ig and anti human PD-1-Ig, PBS were separately co-cultured with peripheral T lymphocytes of cervical cancer patients which stimulated by PHA. FCM was employed to detect the T lymphocytes＇ apoptosis rate and the rate of CD8＋ T/CD4＋ T. Results：There was no PD-L1 expression in normal cervical tissue. In all cervical cancer cases,the PD-L1 normal expression rate was 70%. Statistical analysis showed that PD-L1 expression was significantly associated with cancer cell invasion in cervical carcinomas （ P 〈 0. 05 ）. The number of tumor infiltrating CD8 ~ T cells was significantly reduced in PD-L1 positive cases. Apoptosis occurred in partial tumor infiltrating lymphocytes of PD-L1 positive cervical carcinomas. The apoptotic rates of T cells which co-cultured with human PD-L1-Ig only was higher, there was 32.7 %, CD8＋ T/CD4＋ T rate was 0. 864. Conclusion PD-L1 is expressed aberrantly and closely associated with the invasion of cervical cancer. The expression of PD-L1 is correlated with the reduced number of tumor infiltrating T cells. PD-L1 positive cervical carcinoma can promote active of T lymphocytes,especially CD8＋T cell apoptosis.