表观遗传学
生物
细胞生物学
T细胞
免疫系统
细胞代谢
嵌合抗原受体
效应器
糖酵解
新陈代谢
免疫学
生物化学
基因
作者
Behnia Akbari,Zahra Hosseini,Pardis Shahabinejad,Saba Ghassemi,Hamid Reza Mirzaei,Roddy S. O’Connor
出处
期刊:Cancer Letters
[Elsevier]
日期:2022-12-01
卷期号:550: 215948-215948
被引量:4
标识
DOI:10.1016/j.canlet.2022.215948
摘要
Longevity, functionality, and metabolic fitness are key determinants of chimeric antigen receptor (CAR) T cell efficacy. Activated T cells follow an ordered differentiation program which is facilitated by metabolic adaptations. In response to antigen, T cells undergo a highly-regulated shift to glycolysis. Committing to, and engaging in, glycolysis supports T cell expansion and effector function. Inside tumors, heightened tumor cell metabolism and dysregulated perfusion create a competition for nutrients. As local metabolism supports the differentiation of T cells into functionally-competent progeny, nutrient depletion coupled with persisting antigen can trigger T cell exhaustion. Emerging insights into the barriers impeding CAR T cell function in hostile tumor microenvironments (TME) reveal that metabolic intermediates shape the immune response by influencing epigenetic programs and the control of gene expression. In this review, we discuss recent progress connecting cellular metabolism with epigenetic states in CAR T cells. Given that CAR T cell metabolism can be dynamically regulated, we introduce the concepts of "metabolic-based epigenetic altering" and "epigenetic-based metabolism altering" to restore functional competence in CARTs traversing solid TMEs.
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