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- doi: 10.1038/s41423-020-0365-3
- issn: 1672-7681
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info:eu-repo/semantics/altIdentifier/doi/10.1038/s41423-020-0365-3
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info:eu-repo/semantics/altIdentifier/pmid/32055005
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info:eu-repo/semantics/altIdentifier/eissn/2042-0226
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_D554C59D6F3C0
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N. Dumauthioz et al., « Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity. », Serveur académique Lausannois, ID : 10.1038/s41423-020-0365-3
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Memory CD8 T cells can provide long-term protection against tumors, which depends on their enhanced proliferative capacity, self-renewal and unique metabolic rewiring to sustain cellular fitness. Specifically, memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic demands. In contrast, tumor-infiltrating lymphocytes (TILs) display severe metabolic defects, which may underlie their functional decline. Here, we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), the master regulator of mitochondrial biogenesis (MB), favors CD8 T cell central memory formation rather than resident memory generation. PGC-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide vaccination. Importantly, CD8 T cells with enhanced PGC-1α expression provide stronger antitumor immunity in a mouse melanoma model. Moreover, TILs overexpressing PGC-1α maintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free host. Altogether, our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation, metabolic fitness, and antitumor immunity in vivo.