Combination therapy of HIFα inhibitors and Treg depletion strengthen the anti-tumor immunity in mice.
Eur J Immunol
; 53(12): e2250182, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37615189
ABSTRACT
Hypoxia-inducible factor 1 alpha (HIF1α), under hypoxic conditions, is known to play an oxygen sensor stabilizing role by exerting context- and cell-dependent stimulatory and inhibitory functions in immune cells. Nevertheless, how HIF1α regulates T cell differentiation and functions in tumor settings has not been elucidated. Herein, we demonstrated that T-cell-specific deletion of HIF1α improves the inflammatory potential and memory phenotype of CD8+ T cells. We validated that T cell-specific HIF1α ablation reduced the B16 melanomas development with the indication of ameliorated antitumor immune response with enhanced IFN-γ+ CD8+ T cells despite the increase in the Foxp3+ regulatory T-cell population. This was further verified by treating tumor-bearing mice with a HIF1α inhibitor. Results indicated that HIF1α inhibitor also recapitulates HIF1α ablation effects by declining tumor growth and enhancing the memory and inflammatory potential of CD8+ T cells. Furthermore, a combination of Treg inhibitor with HIF1α inhibitor can substantially reduce tumor size. Collectively, these findings highlight the notable roles of HIF1α in distinct CD8+ T-cell subsets. This study suggests the significant implications for enhancing the potential of T cell-based antitumor immunity by combining HIF1α and Tregs inhibitors.
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Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
/
Linfócitos T Reguladores
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2023
Tipo de documento:
Article