| First Author | St Paul M | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 12 | Pages | 2415-2427.e6 |
| PubMed ID | 34879240 | Mgi Jnum | J:325192 |
| Mgi Id | MGI:6875511 | Doi | 10.1016/j.cmet.2021.11.010 |
| Citation | St Paul M, et al. (2021) Coenzyme A fuels T cell anti-tumor immunity. Cell Metab 33(12):2415-2427.e6 |
| abstractText | Metabolic programming is intricately linked to the anti-tumor properties of T cells. To study the metabolic pathways associated with increased anti-tumor T cell function, we utilized a metabolomics approach to characterize three different CD8(+) T cell subsets with varying degrees of anti-tumor activity in murine models, of which IL-22-producing Tc22 cells displayed the most robust anti-tumor activity. Tc22s demonstrated upregulation of the pantothenate/coenzyme A (CoA) pathway and a requirement for oxidative phosphorylation (OXPHOS) for differentiation. Exogenous administration of CoA reprogrammed T cells to increase OXPHOS and adopt the CD8(+) Tc22 phenotype independent of polarizing conditions via the transcription factors HIF-1alpha and the aryl hydrocarbon receptor (AhR). In murine tumor models, treatment of mice with the CoA precursor pantothenate enhanced the efficacy of anti-PDL1 antibody therapy. In patients with melanoma, pre-treatment plasma pantothenic acid levels were positively correlated with the response to anti-PD1 therapy. Collectively, our data demonstrate that pantothenate and its metabolite CoA drive T cell polarization, bioenergetics, and anti-tumor immunity. |
