Enforced PGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity.
Cell Mol Immunol
; 18(7): 1761-1771, 2021 07.
Article
em En
| MEDLINE
| ID: mdl-32055005
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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vacinas Anticâncer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article