| First Author | Miska J | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 1 | Pages | 226-237.e4 |
| PubMed ID | 30943404 | Mgi Jnum | J:280100 |
| Mgi Id | MGI:6359025 | Doi | 10.1016/j.celrep.2019.03.029 |
| Citation | Miska J, et al. (2019) HIF-1alpha Is a Metabolic Switch between Glycolytic-Driven Migration and Oxidative Phosphorylation-Driven Immunosuppression of Tregs in Glioblastoma. Cell Rep 27(1):226-237.e4 |
| abstractText | The mechanisms by which regulatory T cells (Tregs) migrate to and function within the hypoxic tumor microenvironment are unclear. Our studies indicate that specific ablation of hypoxia-inducible factor 1alpha (HIF-1alpha) in Tregs results in enhanced CD8(+) T cell suppression versus wild-type Tregs under hypoxia, due to increased pyruvate import into the mitochondria. Importantly, HIF-1alpha-deficient Tregs are minimally affected by the inhibition of lipid oxidation, a fuel that is critical for Treg metabolism in tumors. Under hypoxia, HIF-1alpha directs glucose away from mitochondria, leaving Tregs dependent on fatty acids for mitochondrial metabolism within the hypoxic tumor. Indeed, inhibition of lipid oxidation enhances the survival of mice with glioma. Interestingly, HIF-1alpha-deficient-Treg mice exhibit significantly enhanced animal survival in a murine model of glioma, due to their stymied migratory capacity, explaining their reduced abundance in tumor-bearing mice. Thus HIF-1alpha acts as a metabolic switch for Tregs between glycolytic-driven migration and oxidative phosphorylation-driven immunosuppression. |
