Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.
Anti-tumor immunity
CD8
Memory
Mitochondria
PGC-1α
Journal
Cellular & molecular immunology
ISSN: 2042-0226
Titre abrégé: Cell Mol Immunol
Pays: China
ID NLM: 101242872
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
03
07
2019
accepted:
05
01
2020
pubmed:
15
2
2020
medline:
1
4
2022
entrez:
15
2
2020
Statut:
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.
Identifiants
pubmed: 32055005
doi: 10.1038/s41423-020-0365-3
pii: 10.1038/s41423-020-0365-3
pmc: PMC8245409
doi:
Substances chimiques
Cancer Vaccines
0
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
0
Vaccines, Subunit
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1761-1771Subventions
Organisme : Chinese Academy of Medical Sciences (CAMS)
ID : 2016-I2M-1-005
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : CRSII3_141879
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : Ambizione PZ00P3_168077
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : 31003A_182470
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : NSFC 81971466
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : NSFC 31900645
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