Crosstalk Between Autophagy and Metabolic Regulation of (Car) T Cells: Therapeutic Implications Publisher Pubmed



Panahi Meymandi AR¹ ; Akbari B¹ ; Soltantoyeh T¹ ; Hadjati J¹ ; Klionsky DJ² ; Badie B³ ; Mirzaei HR^{1, 4, 5}
Source: Frontiers in Immunology Published:2023

Abstract

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. Copyright © 2023 Panahi Meymandi, Akbari, Soltantoyeh, Hadjati, Klionsky, Badie and Mirzaei.