PD-1、TIM-3、VISTA在急性髓系白血病患者T细胞上的表达及意义

目的:研究多种负性共刺激分子在急性髓系白血病(AML)患者外周血T细胞上的表达及其对预后的影响。方法:收集初治、完全缓解(CR)、未缓解(NR)AML患者外周血标本,采用流式细胞术检测CD4^+和CD8^+T细胞PD-1、VISTA、TIM-3的表达水平,并收集患者临床资料进行统计分析。结果:初治AML组患者CD4^+和CD8^+T细胞PD-1、VISTA、TIM-3表达水平均较对照组显著增高(P<0.05),CR组CD4^+和CD8^+T细胞PD-1、TIM-3、VISTA表达水平均较初治组及NR组显著降低(P<0.05);初治AML患者CD4^+和CD8^+T细胞TIM-3表达水平与VISTA表达水平正相关(r=0.85,r=0.73);初治AML患者,首次诱导化疗未缓解组及高危组患者CD4^+T细胞PD-1、VISTA表达水平显著上升(P<0.05),高危组CD8^+T细胞TIM-3表达水平显著上升(P<0.05),CBFβ-MYH11突变阳性组CD8^+T细胞VISTA表达水平显著降低(P<0.05)。结论:PD-1、TIM-3、VISTA在AML外周血T细胞上的表达可能参与AML的免疫逃逸,并可能成为急性髓系白血病患者的治疗靶点。

Expression and Significance of PD-1,TIM-3 and VISTA on T Cell of Acute Myeloid Leukemia Patients

Objective:To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia(AML)and its affection on prognosis.Methods:The peripheral blood samples from patients with newly diagnosed AML,complete remission(CR),and no-remission(NR)were collected,the expression levels PD-1、VISTA and TIM-3 in CD4^+and CD8^+T cells were detected by flow cytometry,and the clinical data of patients were analyzed.Results:The expression levels of PD-1、VISTA and TIM-3 of CD4^+and CD8^+T cells in the newly diagnosed AML patients were significantly higher than those in control group(P<0.05).The expression levels of PD-1、TIM-3 and VISTA of CD4^+and CD8^+T cells in the CR group were significantly lower than those in newly diagnosed and the NR group(P<0.05).The TIM-3 expression level positively correlated with VISTA expression level of CD4^+and CD8^+T cells in newly diagnosed AML patients(r=0.85 and 0.73).The VISTA and PD-1 expression level of CD4^+T cells in newly diagnosed AML,NR after first induction chemotherapy and high risk patients significantly increased(P<0.05),the TIM-3 expression level of CD8^+T cells in high risk group significantly increased(P<0.05),and the VISTA expression level of CD8^+T cells in CBFβ-MYH11 mutation-positive group significantly decreased(P<0.05).Conclusion:The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.