Vitamin B6 metabolism determines T cell anti-tumor responses was written by Bargiela, David;Cunha, Pedro P.;Velica, Pedro;Foskolou, Iosifina P.;Barbieri, Laura;Rundqvist, Helene;Johnson, Randall S.. And the article was included in Frontiers in Immunology in 2022.Category: pyridine-derivatives The following contents are mentioned in the article:
Targeting T cell metabolism is an established method of immunomodulation. Following activation, T cells engage distinct metabolic programs leading to the uptake and processing of nutrients that determine cell proliferation and differentiation. Redirection of T cell fate by modulation of these metabolic programs has been shown to boost or suppress immune responses in vitro and in vivo. Using publicly available T cell transcriptomic and proteomic datasets we identified vitamin B6-dependent transaminases as key metabolic enzymes driving T cell activation and differentiation. Inhibition of vitamin B6 metabolism using the pyridoxal 5′-phosphate (PLP) inhibitor, aminoxyacetic acid (AOA), suppresses CD8+ T cell proliferation and effector differentiation in a dose-dependent manner. We show that pyridoxal phosphate phosphatase (PDXP), a neg. regulator of intracellular vitamin B6 levels, is under the control of the hypoxia-inducible transcription factor (HIF1), a central driver of T cell metabolism Furthermore, by adoptive transfer of CD8 T cells into a C57BL/6 mouse melanoma model, we demonstrate the requirement for vitamin B6-dependent enzyme activity in mediating effective anti-tumor responses. Our findings show that vitamin B6 metabolism is required for CD8+ T cell proliferation and effector differentiation in vitro and in vivo. Targeting vitamin B6 metabolism may therefore serve as an immunodulatory strategy to improve anti-tumor immunotherapy. This study involved multiple reactions and reactants, such as (4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7Category: pyridine-derivatives).
(4-Formyl-5-hydroxy-6-methylpyridin-3-yl)methyl dihydrogen phosphate (cas: 54-47-7) belongs to pyridine derivatives. In contrast to benzene, Pyridine’s electron density is not evenly distributed over the ring, reflecting the negative inductive effect of the nitrogen atom. Pyridine derivatives are also useful as small-molecule α-helix mimetics that inhibit protein-protein interactions, as well as functionally selective GABA ligands.Category: pyridine-derivatives