| Téléchargement | - Voir la version finale : Coenzyme A fuels T cell anti-tumor immunity (PDF, 3.6 Mio)
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| DOI | Trouver le DOI : https://doi.org/10.1016/j.cmet.2021.11.010 |
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| Auteur | Rechercher : St. Paul, Michael; Rechercher : Saibil, Samuel D.; Rechercher : Han, SeongJun; Rechercher : Israni-Winger, Kavita; Rechercher : Lien, Scott C.; Rechercher : Laister, Rob C.; Rechercher : Sayad, Azin; Rechercher : Penny, Susanne1; Rechercher : Amaria, Rodabe N.; Rechercher : Haydu, Lauren E.; Rechercher : Garcia-Batres, Carlos R.; Rechercher : Mulder, David T.; Rechercher : Robert-Tissot, Céline; Rechercher : Gold, Matthew J.; Rechercher : Tran, Charles W.; Rechercher : Elford, Alisha R.; Rechercher : Nguyen, Linh T.; Rechercher : Pugh, Trevor J.; Rechercher : Pinto, Devanand M.1; Rechercher : Wargo, Jennifer A.; Rechercher : Ohashi, Pamela S. |
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| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | coenzyme A; pantothenate; immunometabolism; CD8+ T cells; Tc12; Tc17; Tc22; immunotherapy; anti-PD1; IL-22 |
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| Résumé | 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. |
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| Date de publication | 2021-12-07 |
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| Maison d’édition | Elsevier |
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| Licence | |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Identificateur | S1550413121005386 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 914905d9-0485-48e5-990f-bc480de59df3 |
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| Enregistrement créé | 2024-03-06 |
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| Enregistrement modifié | 2024-03-06 |
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