Abstract
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-1α 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.
Original language | English (US) |
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Pages (from-to) | 2415-2427.e6 |
Journal | Cell Metabolism |
Volume | 33 |
Issue number | 12 |
DOIs | |
State | Published - Dec 7 2021 |
Keywords
- CD8 T cells
- IL-22
- Tc1
- Tc17
- Tc22
- anti-PD1
- coenzyme A
- immunometabolism
- immunotherapy
- pantothenate
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology