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Mitochondrial isocitrate dehydrogenase impedes CAR T cell function by restraining antioxidant metabolism and histone acetylation.
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ID: paper-38171332
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Mitochondrial isocitrate dehydrogenase impedes CAR T cell function by restraining antioxidant metabolism and histone acetylation.
Si X, Shao M, Teng X, Huang Y, Meng Y, Wu L, Wei J, Liu L, Gu T, Song J, Jing R, Zhai X, Guo X, Kong D, Wang X, Cai B, Shen Y, Zhang Z, Wang D, Hu Y, Qian P, Xiao G, Huang H
Abstract
The efficacy of chimeric antigen receptor (CAR) T cell therapy is hampered by relapse in hematologic malignancies and by hyporesponsiveness in solid tumors. Long-lived memory CAR T cells are critical for improving tumor clearance and long-term protection. However, during rapid ex vivo expansion or in vivo tumor eradication, metabolic shifts and inhibitory signals lead to terminal differentiation and exhaustion of CAR T cells. Through a mitochondria-related compound screening, we find that the FD...
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