| First Author | Wei P | Year | 2023 |
| Journal | Eur J Immunol | Volume | 53 |
| Issue | 12 | Pages | e2250182 |
| PubMed ID | 37615189 | Mgi Jnum | J:352774 |
| Mgi Id | MGI:7574777 | Doi | 10.1002/eji.202250182 |
| Citation | Wei P, et al. (2023) Combination therapy of HIFalpha inhibitors and Treg depletion strengthen the anti-tumor immunity in mice. Eur J Immunol 53(12):e2250182 |
| abstractText | Hypoxia-inducible factor 1 alpha (HIF1alpha), 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 HIF1alpha regulates T cell differentiation and functions in tumor settings has not been elucidated. Herein, we demonstrated that T-cell-specific deletion of HIF1alpha improves the inflammatory potential and memory phenotype of CD8(+) T cells. We validated that T cell-specific HIF1alpha ablation reduced the B16 melanomas development with the indication of ameliorated antitumor immune response with enhanced IFN-gamma(+) CD8(+) T cells despite the increase in the Foxp3(+) regulatory T-cell population. This was further verified by treating tumor-bearing mice with a HIF1alpha inhibitor. Results indicated that HIF1alpha inhibitor also recapitulates HIF1alpha ablation effects by declining tumor growth and enhancing the memory and inflammatory potential of CD8(+) T cells. Furthermore, a combination of Treg inhibitor with HIF1alpha inhibitor can substantially reduce tumor size. Collectively, these findings highlight the notable roles of HIF1alpha in distinct CD8(+) T-cell subsets. This study suggests the significant implications for enhancing the potential of T cell-based antitumor immunity by combining HIF1alpha and Tregs inhibitors. |
