靶向抑制PD-1/PD-L1信号通路在嵌合抗原受体T细胞免疫治疗血液肿瘤中的研究现状

Research progress on inhibiting PD-1/PD-L1 signaling pathway in treatment of hematologic malignancies by chimeric antigen receptor T-cell immunotherapy

嵌合抗原受体T细胞(CAR-T)免疫疗法已在治疗血液肿瘤方面已取得巨大成功,然而大部分患者在接受CAR-T免疫治疗后复发,复发的主要原因之一是CAR-T耗竭。研究发现,CAR-T耗竭和程序性死亡受体(PD)-1的持续表达,以及与PD配体(PD-L)1的相互作用有关。靶向抑制PD-1/PD-L1信号通路可以部分逆转CAR-T耗竭的状态,提高CAR-T抗肿瘤活性。笔者拟就PD-1/PD-L1信号通路参与肿瘤免疫逃逸,抑制CAR-T抗肿瘤活性,以及靶向抑制PD-1/PD-L1信号通路联合CAR-T免疫疗法治疗血液肿瘤的基础研究和临床试验等方面的研究现状进行总结。

Chimeric antigen receptor T-cell(CAR-T)immunotherapy have achieved great success in treatment of hematological malignancies,but most patients relapse after CAR-T immunotherapy,and one of the main causes of relapse is CAR-T exhaustion.Studies have found that CAR-T exhaustion is associated with sustained programmed cell death receptor(PD)-1 expression and interaction with PD ligand(PD-L)1.Inhibiting PD-1/PD-L1 signaling pathway can partially reverse the exhaustion of CAR-T and improve anti-tumor activity of CAR-T.This article summarizes the research progress on PD-1/PD-L1 signaling pathway involved in tumor escape,its inhibition role of CAR-T,and preclinical research and clinical trials of targeting PD-1/PD-L1 pathway combined with CAR-T in treatment of hematological malignancies.