The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function
Mathias Wenes, Alison Jaccard, Tania Wyss, Noelia Maldonado‐Pérez, Shao Thing Teoh, Anouk Lepez, Fabrice Renaud, Fabien Franco, Patrice Waridel, Céline Yacoub Maroun, Benjamin Tschumi, Nina Dumauthioz, Lianjun Zhang, Alena Donda, Francisco Martı́n, Denis Migliorini, Sophia Y. Lunt, Ping‐Chih Ho, Pedro Romero
Abstract
T cell antitumor function. We further revealed that chimeric antigen receptor (CAR) T cell manufacturing with an MPC inhibitor imprinted a memory phenotype and demonstrated that infusing MPC inhibitor-conditioned CAR T cells resulted in superior and long-lasting antitumor activity. Altogether, we uncover that mitochondrial pyruvate uptake instructs metabolic flexibility for guiding T cell differentiation and antitumor responses.
Topics & Concepts
Cell biologyGlycolysisPKM2CD8MitochondrionBiologyBeta oxidationGlutamineWarburg effectTumor microenvironmentBiochemistryMetabolismChemistryCancer researchAntigenPyruvate kinaseImmunologyAmino acidTumor cellsCAR-T cell therapy researchImmune Cell Function and InteractionCancer Immunotherapy and Biomarkers