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

Zhonghua Xue Ye Xue Za Zhi. 2017 Mar 14;38(3):198-203. doi: 10.3760/cma.j.issn.0253-2727.2017.03.005.
[Article in Chinese]

Abstract

Objective: To observe the expression levels of PD-1/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 β(2)-MG expression were analyzed. Results: ①Compared with control, CLL patients, including 39 males and 18 females with the median age of (63.7±10.7) 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) . ②In Rai staging, the later the stage, the higher expression of PD-1/PD-L1 (P<0.05) . ③PD-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) . ④The 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 β(2)-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 β(2)-MG. PD-1/PD-L1 may be a prognostic factor in patients with CLL.

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、β(2)微球蛋白(β(2)-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β(2)-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β(2)-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。.

Keywords: Antigens, CD274; Leukemia, lymphocytic, chronic, B-cell; Programmed cell death 1 receptor.

MeSH terms

  • ADP-ribosyl Cyclase 1
  • Aged
  • B7-H1 Antigen
  • CD8-Positive T-Lymphocytes
  • Chromosome Aberrations
  • Female
  • Flow Cytometry
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell*
  • Male
  • Middle Aged
  • Prognosis
  • ZAP-70 Protein-Tyrosine Kinase

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • ZAP-70 Protein-Tyrosine Kinase
  • ZAP70 protein, human
  • ADP-ribosyl Cyclase 1

Grants and funding

基金项目:新疆维吾尔自治区自然科学基金(2013211A100)