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

Détails

Ressource 1Télécharger: 32055005_BIB_D554C59D6F3C.pdf (1775.07 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_D554C59D6F3C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.
Périodique
Cellular & molecular immunology
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
07/2021
Peer-reviewed
Oui
Volume
18
Numéro
7
Pages
1761-1771
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
17/02/2020 17:51
Dernière modification de la notice
12/04/2022 6:34
Données d'usage