T cell senescence and CAR-T cell exhaustion in hematological malignancies

被引:203
作者
Kasakovski, Dimitri [1 ,2 ]
Xu, Ling [1 ,3 ]
Li, Yangqiu [1 ,3 ]
机构
[1] Jinan Univ, Key Lab Regenerat Med, Minist Educ, Inst Hematol,Sch Med, Guangzhou 510632, Guangdong, Peoples R China
[2] Ruhr Univ Bochum, Dept Anat & Mol Embryol, Inst Anat, D-44801 Bochum, Germany
[3] Jinan Univ, Dept Hematol, Affiliated Hosp 1, Sch Med, 601 West Huangpu Ave, Guangzhou 510632, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
T cells; Senescence; Hematological malignancy; T cell activation; CAR-T cells; UMBILICAL-CORD BLOOD; IMMUNE MODULATION; REPLICATIVE SENESCENCE; REGENERATIVE THERAPY; 4-1BB COSTIMULATION; ENVIRONMENTAL CUES; TUMOR-IMMUNITY; CANCER; TRANSPLANTATION; INDUCTION;
D O I
10.1186/s13045-018-0629-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
T cell senescence has been recognized to play an immunosuppressive role in the aging population and cancer patients. Strategies dedicated to preventing or reversing replicative and premature T cell senescence are required to increase the lifespan of human beings and to reduce the morbidity from cancer. In addition, overcoming the T cell terminal differentiation or senescence from lymphoma and leukemia patients is a promising approach to enhance the effectiveness of adoptive cellular immunotherapy (ACT). Chimeric antigen receptor T (CAR-T) cell and T cell receptor-engineered T (TCR-T) cell therapy highly rely on functionally active T cells. However, the mechanisms which drive T cell senescence remain unclear and controversial. In this review, we describe recent progress for restoration of T cell homeostasis from age-related senescence as well as recovery of T cell activation in hematological malignancies.
引用
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页数:9
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