Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_D554C59D6F3C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.
Journal
Cellular & molecular immunology
Author(s)
Dumauthioz N., Tschumi B., Wenes M., Marti B., Wang H., Franco F., Li W., Lopez-Mejia I.C., Fajas L., Ho P.C., Donda A., Romero P., Zhang L.
ISSN
2042-0226 (Electronic)
ISSN-L
1672-7681
Publication state
Published
Issued date
07/2021
Peer-reviewed
Oui
Volume
18
Number
7
Pages
1761-1771
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Animals, CD8-Positive T-Lymphocytes/metabolism, Cancer Vaccines, Mice, Mitochondria/metabolism, Organelle Biogenesis, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism, Vaccines, Subunit, Anti-tumor immunity, CD8, Memory, Mitochondria, PGC-1α
Pubmed
Web of science
Open Access
Yes
Create date
17/02/2020 17:51
Last modification date
12/04/2022 6:34
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