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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 HR1, 4, 5
Authors
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Authors Affiliations
  1. 1. Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, United States
  3. 3. Division of Neurosurgery, City of Hope Beckman Research Institute, Duarte, CA, United States
  4. 4. Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States
  5. 5. Institute for Immunology and Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States

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.
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