共抑制分子TIGIT/CD155和PD-1在慢性淋巴细胞白血病中的表达及临床意义  

Expression and Clinical Significance of Co-inhibitory Molecules TIGIT/CD155 and PD-1 in Chronic Lymphocytic Leukemia

作　　者：张瑞[1] 陈双[1] 骆婷婷 曲建华[1] ZHANG Rui;CHEN Shuang;LUO Ting-Ting;QU Jian-Hua(Laboratory of Hematology Center,The First Afiliated Hospital of Xinjiang Medical Universiry,Hematology Institute of Xinjiang Uygur Autonomous Region,Urumqi 830054,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学第一附属医院血液病中心实验室,新疆维吾尔自治区血液病研究所,新疆乌鲁木齐830054

出　　处：《中国实验血液学杂志》2025年第1期54-61,共8页Journal of Experimental Hematology

基　　金：新疆维吾尔自治区天山创新团队(2022D14008)。

摘　　要：目的:探讨共抑制分子TIGIT/CD155和PD-1在慢性淋巴细胞白血病(CLL)患者外周血CD4^(+)T细胞和Treg细胞上的表达,并分析其临床意义。方法:选取40例CLL患者和20例健康人员,采用流式细胞术检测CD4^(+)T细胞和Treg细胞表面抑制性分子PD-1、TIGIT的表达水平,并检测受试者外周血B细胞和DC细胞上CD155的表达水平。结果:CLL患者组外周血PD-1^(+)TIGIT^(+)CD4^(+)T细胞、PD-1^(+)TIGIT^(+)Treg细胞、CD155^(+)DC细胞比例均明显高于健康对照组(P<0.05)。CLL患者的PD-1^(+)TIGIT^(+)CD4^(+)T细胞和PD-1^(+)TIGIT^(+)Treg细胞比例均明显高于PD-1^(+)TIGIT-CD4^(+)T细胞和PD-1^(+)TIGIT-Treg细胞(P<0.05)。PD-1^(+)TIGIT^(+)CD4^(+)T细胞和PD-1^(+)TIGIT^(+)Treg细胞均与CD155^(+)DC细胞水平呈正相关(r=0.742,r=0.766)。随着Binet分期进展,PD-1^(+)TIGIT^(+)CD4^(+)T细胞、PD-1^(+)TIGIT^(+)Treg细胞、CD155^(+)DC细胞比例逐渐增加(P<0.05),CD38≥30%、IGVH未突变、染色体异常的预后不良组患者的上述三种细胞比例均增高(P<0.05)。结论:PD-1和TIGIT共抑制分子可能参与了CLL晚期患者的免疫耗竭,具有临床预后参考价值。双抑制分子靶向治疗为CLL个体化治疗提供了新的方向。Objective:To investigate the expression of co-inhibitory molecules TIGIT/CD155 and PD-1 on CD4^(+)T cells and Treg cells in peripheral blood of patients with chronic lymphocytic leukemia(CLL)and analyze their clinical significance.Methods:The expression of PD-1 and TIGIT on CD4^(+)T cells and Treg cells was detected by flow cytometry in 40 CLL patients and 20 healthy controls.Additionally,the expression of CD 155 on peripheral blood B cells and DC cells of the enrolled subjects was detected.Results:The proportions of PD-1^(+)TIGIT^(+)CD4^(+)T cells,PD-1^(+)TIGIT^(+)Treg cells and CD155^(+)DC cells in peripheral blood of CLL patients were significantly higher than those of healthy controls(P<0.05).The proportions of PD-1^(+)TIGIT^(+)CD4^(+)T cells and PD-1^(+)TIGIT^(+)Treg cells in CLL patients were significantly higher than those of PD-1^(+)TIGIT-CD4^(+)T cells and PD-1^(+)TIGIT-Treg cells,respectively(P<0.05).Both PD-1^(+)TIGIT^(+)CD4^(+)T cells and PD-1^(+)TIGIT^(+)Treg cells were positively correlated with the level of CD155^(+)DC cells(r=0.742,r=0.766).With the progression of Binet stage,the proportions of PD-1^(+)TIGIT^(+)CD4^(+)T cells,PD-1^(+)TIGIT^(+)Treg cells,and CD155^(+)DC cells gradually increased(P<0.05),and the aforementioned three types cells were all increased in patients with CD38≥30%,IGVH unmutated,or poor prognosis due to chromosomal abnormalities(P<0.05).Conclusion:Co-inhibitory molecules PD-1 and TIGIT may be involved in immunodepletion in patients with advanced CLL,which has clinical prognostic value.Dual inhibitor molecular targeted therapy provides a new direction for the individualized treatment of CLL.

关 键 词：慢性淋巴细胞白血病 抑制性分子 PD-1 TIGIT 

分 类 号：R733.72[医药卫生—肿瘤]