程序性死亡受体1与其配体在T淋巴母细胞淋巴瘤/白血病中的表达及其临床意义

Expression of programmed death 1 and programmed death-ligand 1 in T-lymphoblastic lymphoma/leukemia and their clinical significances

目的 研究程序性死亡受体1（PD-1）与程序性死亡配体1（PD-L1）在T淋巴母细胞淋巴瘤/白血病（T-LBL/ALL）中的表达情况,探讨两者的表达与患者临床病理特征及预后的关系.方法 应用免疫组织化学法（IHC）及实时荧光定量聚合酶链反应（qRT-PCR）对56例T-LBL/ALL（实验组）和20例淋巴结反应性增生（LH）（对照组）组织中PD-1与PD-L1表达水平进行检测.结果 IHC结果：PD-1在T-LBL/ALL肿瘤细胞不表达,在肿瘤浸润免疫细胞的阳性表达率为17.9 %（10/56）,与对照组（90.0 %,18/20）相比,差异具有统计学意义（P=0.000）.PD-L1蛋白在实验组和对照组的阳性率分别为37.5 %（21/56）和10.0 %（2/20）,两组间比较差异具有统计学意义（P=0.044）.qRT-PCR结果：T-LBL/ALL组中PD-L1 和PD-1 mRNA相对表达量均高于对照组（12.255比2.575;37.990比3.615）,差异均有统计学意义（P〈0.05）.单因素分析：年龄、PD-L1蛋白和mRNA表达水平与预后有关（P〈0.05）.多因素Cox回归分析：PD-L1蛋白高表达及患者年龄≤25岁为独立的预后危险因素（P〈0.05）.结论 PD-1/PD-L1可能参与T-LBL/ALL的免疫逃逸,有望成为治疗T-LBL/ALL新的靶点.

Objective To study the expression of programmed death 1 （PD-1） and its ligand PD-L1 in T lymphoblastic lymphoma/leukemia （T-LBL/ALL）, and to explore the relationship between their expression and clinical pathological factors and prognosis of the disease. Methods PD-L1 and PD-1 were detected in 56 patients with T-LBL/ALL by immunohistochemistry and quantitative real-time polymerase chain reaction （qRT-PCR）. Twenty patients with reactive hyperplasia were selected as the control group. Results Immunohistochemical results showed that PD-1 was not expressed in T-LBL/ALL tumor cells and 17.9 %（10/56） in tumor infiltrating immune cells,which was statistically significant compared with control group（18/20,90 %） （P= 0.000）. The positive rates of PD-L1 protein were 37.5 % （21/56） and 10.0 % （2/20） in the experimental group and the control group, respectively and accordingly the difference between the two groups was statistically significant （P =0.044）. Results of qRT-PCR showed that the relative expression levels of PD-L1 and PD-1 mRNA in 56 cases of T-LBL/ALL were significantly higher than those in control group （12.255 vs. 2.575, 37.990 vs. 3.615）, and the differences were both statistically significant （both P 〈 0.05）. Univariate analysis showed that age, PD-L1 protein and mRNA expression were closely correlated with prognosis（all P 〈0.05）. Multivariate Cox regression analysis showed that overexpression of PD-L1 protein and age （≤25 years old）were independent prognostic risk factors（both P 〈0.05）.Conclusion In T-LBL/ALL,PD-1/PD-L1 may be involved in the immune escape of the tumor,which is expected to be a new target for the treatment of diseases.