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自噬与 CAR-T 细胞代谢调控之间的交互作用:治疗意义

英文原题:Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.

查看英文原题

Crosstalk between autophagy and metabolic regulation of (CAR) T cells: therapeutic implications.

PubMed 2023/08/22(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

尽管嵌合抗原受体(CAR)T 细胞疗法治疗部分 B 细胞淋巴瘤和白血病取得非凡成功,多种障碍仍限制其在实体瘤中的应用,因此研究人员开始探索能够制备治疗潜力更强 CAR-T 细胞的新方法。关于 CAR-T 临床疗效障碍的新认识显示,自噬可通过重编程细胞代谢塑造免疫应答,反之亦然。自噬是一种细胞“自我消化”过程,在溶酶体中降解和回收细胞内成分,并影响 T 细胞生物学,包括发育、存活、记忆形成和细胞代谢。本综述重点讨论自噬在调节和重塑 CAR-T 细胞代谢回路中的关键作用,以及 CAR-T 细胞和肿瘤微环境(TME)的代谢状态如何改变 CAR-T 细胞的自噬调控,从而恢复其在实体瘤 TME 中穿行时的功能能力。

展开英文摘要原文

Despite chimeric antigen receptor (CAR) T cell therapy's extraordinary success in subsets of B-cell lymphoma and leukemia, various barriers restrict its application in solid tumors. This has prompted investigating new approaches for producing CAR T cells with superior therapeutic potential. Emerging insights into the barriers to CAR T cell clinical success indicate that autophagy shapes the immune response via reprogramming cellular metabolism and vice versa.

Autophagy, a self-cannibalization process that includes destroying and recycling intracellular components in the lysosome, influences T cell biology, including development, survival, memory formation, and cellular metabolism. In this review, we will emphasize the critical role of autophagy in regulating and rewiring metabolic circuits in CAR T cells, as well as how the metabolic status of CAR T cells and the tumor microenvironment (TME) alter autophagy regulation in CAR T cells to restore functional competence in CAR Ts traversing solid TMEs.

论文信息

作者
Panahi Meymandi AR、Akbari B、Soltantoyeh T、Hadjati J、Klionsky DJ、Badie B、Mirzaei HR
单位
Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Iran
文献类型
综述 · 非美国政府资助研究
期刊
Frontiers in immunology2023
原文标识
PubMed 37675121 · DOI 10.3389/fimmu.2023.1212695