| Download | - View final version: Coenzyme A fuels T cell anti-tumor immunity (PDF, 3.6 MiB)
|
|---|
| DOI | Resolve DOI: https://doi.org/10.1016/j.cmet.2021.11.010 |
|---|
| Author | Search for: St. Paul, Michael; Search for: Saibil, Samuel D.; Search for: Han, SeongJun; Search for: Israni-Winger, Kavita; Search for: Lien, Scott C.; Search for: Laister, Rob C.; Search for: Sayad, Azin; Search for: Penny, Susanne1; Search for: Amaria, Rodabe N.; Search for: Haydu, Lauren E.; Search for: Garcia-Batres, Carlos R.; Search for: Mulder, David T.; Search for: Robert-Tissot, Céline; Search for: Gold, Matthew J.; Search for: Tran, Charles W.; Search for: Elford, Alisha R.; Search for: Nguyen, Linh T.; Search for: Pugh, Trevor J.; Search for: Pinto, Devanand M.1; Search for: Wargo, Jennifer A.; Search for: Ohashi, Pamela S. |
|---|
| Affiliation | - National Research Council of Canada. Human Health Therapeutics
|
|---|
| Format | Text, Article |
|---|
| Subject | coenzyme A; pantothenate; immunometabolism; CD8+ T cells; Tc12; Tc17; Tc22; immunotherapy; anti-PD1; IL-22 |
|---|
| 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-1a 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. |
|---|
| Publication date | 2021-12-07 |
|---|
| Publisher | Elsevier |
|---|
| Licence | |
|---|
| In | |
|---|
| Language | English |
|---|
| Peer reviewed | Yes |
|---|
| Identifier | S1550413121005386 |
|---|
| Export citation | Export as RIS |
|---|
| Report a correction | Report a correction (opens in a new tab) |
|---|
| Record identifier | 914905d9-0485-48e5-990f-bc480de59df3 |
|---|
| Record created | 2024-03-06 |
|---|
| Record modified | 2024-03-06 |
|---|
