T细胞衰老在血液系统恶性肿瘤及其免疫治疗中的研究进展

Research Progress of T Cell Senescence and Its Relevance to Immunotherapy in Hematological Malignancies

衰老T细胞是一类缺乏抗原特异性反应的分化增殖末期的淋巴细胞。肿瘤细胞可以诱导T细胞衰老,衰老T细胞的增殖能力被抑制和表现出衰老相关分泌表型(senescence-associated secretory phenotype,SASP),从而抑制机体免疫能力。血液系统恶性肿瘤患者的免疫功能常受损,常规治疗后有复发风险。免疫检查点抑制剂(immune checkpoint inhibitor,ICI)和嵌合抗原受体基因修饰T细胞(chimeric antigen receptor T cell,CAR-T)等免疫疗法在部分血液系统肿瘤中显示出较好的应用前景,然而T细胞衰老可能是部分免疫疗法治疗失败的潜在原因,阻断和恢复T细胞衰老的治疗方案可能是协同增强肿瘤免疫治疗的关键目标。全文对T细胞衰老的特征和机制,以及T细胞衰老在血液系统恶性肿瘤中的表达及治疗策略进行综述。

Senescent T cells are lymphocytes at terminal stage of proliferation and differentiation lacking antigen-specific response.Tumor cells can induce T cell senescence,and the proliferation of senescent T cells is inhibited showing senescence-associated secretory phenotype(SASP),leading to immunological potential inhibition in the body.Patients with hematological malignancies frequently have impaired immune systems with high risk of recurrence after routine treatment.Immunotherapy,such as checkpoint inhibitor(ICI) therapy,chimeric antigen receptor T cell(CAR-T) therap,has shown excellent clinical efficacy in some hematological malignancies.However,T cell senescence would be a potential factor in the failure of some immunotherapies,therefore,preventing and reversing T cell senescence may elicit synergistic effect for tumor immunotherapy.This article reviews the characteristics and mechanisms of T cell senescence,its expression in hematological malignancies and the relevance to therapeutic strategies.