Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, United States.
Front Immunol. 2023 Aug 22;14:1212695. doi: 10.3389/fimmu.2023.1212695. eCollection 2023.
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.
尽管嵌合抗原受体 (CAR) T 细胞疗法在 B 细胞淋巴瘤和白血病亚组中取得了非凡的成功，但各种障碍限制了其在实体瘤中的应用。这促使人们研究具有更好治疗潜力的 CAR T 细胞的新方法。对 CAR T 细胞临床成功障碍的新认识表明，自噬通过重塑细胞代谢来塑造免疫反应，反之亦然。自噬是一种自我吞噬过程，包括在溶酶体中破坏和回收细胞内成分，它影响 T 细胞生物学，包括发育、存活、记忆形成和细胞代谢。在这篇综述中，我们将强调自噬在调节和重编 CAR T 细胞代谢回路中的关键作用，以及 CAR T 细胞的代谢状态和肿瘤微环境 (TME) 如何改变 CAR T 细胞中的自噬调节，以恢复在实体 TME 中穿行的 CAR T 细胞的功能能力。
