PD-1／PD—L1共刺激分子在慢性淋巴细胞白血病患者中的表达及临床意义

PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia

目的观察程序性死亡受体1／及其配体（PD-1／PD-L1）共刺激分子在慢性淋巴细胞白血病（CLL）患者中的表达水平，并探讨其可能的临床意义。方法以57例CLL患者为研究对象，以20名健康体检者为对照，采用流式细胞术分别检测其外周血CD8＋、CD4＋T细胞和CD19＋B细胞中PD-1的表达水平，以及树突细胞（DC）中PD—L1的表达水平；同时分析PD-1／PD—L1表达与疾病分期、CD38表达、ZAP-70表达、染色体核型异常、β2微球蛋白（β2-MG）表达水平的相关性。结果①CLL患者组中男39例，女18例，平均年龄（63．7±10．7）岁。与对照组比较，年龄、性别差异无统计学意义（P值均〉0．05）；CLL患者组外周血中PD-1、PD—L1的表达均高于对照组（P值均〈0．05）。②在Rai分期低、中、高危组中，随着危险度的增高PD-1、PD—L1的表达水平亦增高（P值均〈0．05）。③PD-1表达在CD8＋CD38＋组（11例）高于CD8＋CD38-组（46例）（P=0．004），在CD8＋预后不良染色体组（14例）高于CD8＋预后良好染色体组（28例）（P=0．004）。④PD—L1表达在CD38＋组（11例）高于CD38组（46例）（P=0．002），在ZAP-70＋组（11例）高于ZAP-70组（28例）（P〈0．001），在预后不良染色体组（14例）高于预后良好染色体组（28例）（P=0．023）。PD-1、PD—L1表达与β2-MG表达无相关性（P值均〉0．05）。结论PD-1、PD—L1在CLL患者体内存在高表达，其表达水平与疾病分期、CD38表达、ZAP-70表达、染色体核型等预后指标存在一定的相关性，与β2-MG表达无相关性，提示其有可能作为评估CLL患者预后的指标。

Objective To observe the expression levels of PD-I/PD-L1 costimulatory molecules and explore the clinical significance in patients with chronic lymphocytic leukemia （CLL）. Methods The expression of PD-1/PD-L1 in peripheral blood CD8＋T cells, CD4＋T cells, CD19＋B, and dendrites cells （DC） was detected by flow cytometry in 57 CLL patients and 20 healthy controls. The correlations of PD-1/ PD-L1 expression with disease stage, CD38 expression, ZAP-70 expression, chromosome karyotype abnormality and 132-MG expression were analyzed. Results （1） Compared with control, CLL patients, including 39 males and 18 females with the median age of （63.7±0.7） years, had no statistically significant difference in age and gender （P〉0.05）. CLL patients had the higher PD-1/PD-L1 expression than healthy controls （P〈0.05）. Gin Rai staging, the later the stage, the higher expression of PD-I/PD-L1 （P〈0.05）. （3）PD- 1 expression in CD8＋CD38＋ group （ 11 cases） was higher than that in CD8＋CD38- group （46 cases） （P=0.004）, and CD8＋poor prognosis chromosome group （ 14 cases） also had significant higher PD-1 expression than CD8＋good prognosis chromosome group （28 cases） （P=0.004）. （4）The expression of PD-L1 was higher in CD38＋group, ZAP-70＋group, and poor prognosis group, as compared to that in CD38- group （P=0.002）, in ZAP-70 group （P〈0.001）, in good prognosis group （P=-0.023）. There was no correlation between the expression of PD-1/PD-L1 and 132-MG （P〉0.05）. Conclusion This data reveals that PD- 1/PD-L1 was highly expressed in CLL patients. Its expression levels were correlated with Rai stage, CD38, ZAP-70, chromosome karyotype, but not with β2-MG. PD-1/PD-L1 may be a prognostic factor in patients with CLL.