Details

Autor(en) / Beteiligte

• St Paul, Michael
• Saibil, Samuel D
• Han, SeongJun
• Israni-Winger, Kavita
• Lien, Scott C
• Laister, Rob C
• Sayad, Azin
• Penny, Susanne
• Amaria, Rodabe N
• Haydu, Lauren E
• Garcia-Batres, Carlos R
• Kates, Meghan
• Mulder, David T
• Robert-Tissot, Céline
• Gold, Matthew J
• Tran, Charles W
• Elford, Alisha R
• Nguyen, Linh T
• Pugh, Trevor J
• Pinto, Devanand M
• Wargo, Jennifer A
• Ohashi, Pamela S

Titel

Coenzyme A fuels T cell anti-tumor immunity

Ist Teil von

• Cell metabolism, 2021-12, Vol.33 (12), p.2415-2427.e6

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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.