基因工程嵌合抗原受体（CAR）T细胞可以治愈对标准治疗没有反应的癌症患者。迄今为止，免疫细胞治疗在固体肿瘤方面效果较差，主要是由于免疫细胞在抑制免疫肿瘤微环境（TME）中的定位和功能受损。细胞代谢在T细胞功能和存活中发挥关键作用，并且易于操作。本文提供了CAR T代谢已知方面的概述，并描述了操纵CAR T代谢特征以产生更好的抗肿瘤反应的潜在方法。与细胞代谢谱相关的不同T细胞表型与改善的抗肿瘤反应相关。 CAR T制造过程中的几个步骤易于干预，可以产生和维持有利的细胞内代谢表型。例如，共刺激信号是通过代谢重构执行的。在CAR T扩增过程中或在接受移植后系统地使用代谢调节剂，被描述为产生和维持可传递的代谢状态的潜在方法，这可以使T细胞在体内功能和持久性方面获得更好的效果。扩增过程中的细胞因子和营养选择可以定制，以产生具有更有利代谢特征的CAR T产品。总之，更好的了解CAR T细胞代谢以及其操纵有可能指导更有效的免疫细胞治疗的发展。版权所有 ©2023 Nanjireddy，Olejniczak和Buxbaum。

Genetically engineered chimeric antigen receptor (CAR) T cells can cure patients with cancers that are refractory to standard therapeutic approaches. To date, adoptive cell therapies have been less effective against solid tumors, largely due to impaired homing and function of immune cells within the immunosuppressive tumor microenvironment (TME). Cellular metabolism plays a key role in T cell function and survival and is amenable to manipulation. This manuscript provides an overview of known aspects of CAR T metabolism and describes potential approaches to manipulate metabolic features of CAR T to yield better anti-tumor responses. Distinct T cell phenotypes that are linked to cellular metabolism profiles are associated with improved anti-tumor responses. Several steps within the CAR T manufacture process are amenable to interventions that can generate and maintain favorable intracellular metabolism phenotypes. For example, co-stimulatory signaling is executed through metabolic rewiring. Use of metabolic regulators during CAR T expansion or systemically in the patient following adoptive transfer are described as potential approaches to generate and maintain metabolic states that can confer improved in vivo T cell function and persistence. Cytokine and nutrient selection during the expansion process can be tailored to yield CAR T products with more favorable metabolic features. In summary, improved understanding of CAR T cellular metabolism and its manipulations have the potential to guide the development of more effective adoptive cell therapies.Copyright © 2023 Nanjireddy, Olejniczak and Buxbaum.