PD-1、PD-L1和T细胞亚群在膀胱尿路上皮癌中的表达及临床病理特征相关性分析

Expression of PD-1,PD-L1 and T lymphocyte subsets in bladder urothelial carcinoma and their correlation with clinicopathologic features

目的探讨程序性死亡分子1(PD-1)及其配体(PD-L1)和T细胞亚群在膀胱尿路上皮癌中的表达情况及其与临床病理特征相关性分析。方法采用免疫组织化学方法检测70例膀胱尿路上皮癌及癌旁正常尿路上皮组织PD-1、PD-L1、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞阳性表达情况,分析各指标阳性表达情况与临床病理特征的关系,并分析PD-1、PD-L1、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞表达的相关性。结果膀胱尿路上皮癌PD-1、PD-L1、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞的表达均显著高于癌旁正常组织(P<0.05)。高级别、T3~T4期组织中PD-1、PD-L1、CD4^(+)T淋巴细胞、CD8^(+)T淋巴细胞表达分别明显高于低级别、Ta~T2期的组织;肿瘤直径≥3 cm的组织PD-L1表达显著高于肿瘤直径<3 cm的组织(P<0.05)。CD4^(+)淋巴细胞与PD-1、PD-L1、CD8^(+)淋巴细胞表达呈正相关(r=0.257、0.312、0.329,P<0.05),PD-1与PD-L1表达呈正相关(r=0.278,P<0.05)。结论PD-1、PD-L1、CD4^(+)淋巴细胞、CD8^(+)淋巴细胞在膀胱尿路上皮癌中高表达,其表达与组织学级别、浸润深度相关,阻断PD-1/PD-L1信号通路可能成为治疗膀胱尿路上皮癌潜在的靶点。

Objective To investigate the correlation between the expression of PD-1,PD-L1,T lymphocyte subsets and clinicopathologic parameters in bladder urothelial carcinoma(BUC).Methods Tissue samples from 70 patients with BUC and normal bladder tissues were examined for PD-L1,PD-1,CD4^(+)lymphocytes and CD8^(+)lymphocytes expression by immunohistochemical staining.The relationship was analyzed between the positive expression of each indicator and the clinicopathological characteristics and between the expression of PD-L1,PD-1,CD4^(+)lymphocytes and CD8^(+)lymphocytes.Results The expression of PD-L1,PD-1,CD4^(+)lymphocytes and CD8^(+)lymphocytes in bladder urothelial carcinoma was significantly higher than those in para-carcinoma normal tissues(P<0.05).The expression levels of PD-L1,PD-1,CD4^(+)lymphocytes and CD8^(+)T lymphocytes in the tissues of high grade and T3~T4 were significantly higher than that in the tissues of low grade and Ta~T2.The expression of PD-L1 in tissues with tumor diameter≥3 cm was significantly higher than that in tissues with tumor diameter<3 cm(P<0.05).CD4^(+)lymphocytes were positively correlated with the expression of PD-L1,PD-1,CD8^(+)lymphocytes(r=0.257,0.312,0.329,P<0.05),and PD-1 was positively correlated with the expression of PD-L1(r=0.278,P<0.05).Conclusion PD-L1,PD-1,CD4^(+)lymphocytes and CD8^(+)lymphocytes are highly expressed in urothelial carcinoma of the bladder,and their expression is related to histological level and invasion depth.Blocking the PD-1/PD-L1 signaling pathway may become a potential target for the treatment of urothelial carcinoma of the bladder.