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

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.

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

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.