Blockade of 6-phosphogluconate dehydrogenase generates CD8
6-Aminonicotinamide
/ chemistry
Animals
CD8-Positive T-Lymphocytes
/ cytology
Cell Differentiation
Cell Line, Tumor
Granzymes
/ genetics
Humans
Immunotherapy
Listeria monocytogenes
/ physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria
/ metabolism
Neoplasms
/ metabolism
Pentose Phosphate Pathway
/ drug effects
Phosphogluconate Dehydrogenase
/ antagonists & inhibitors
Reactive Oxygen Species
/ metabolism
Signal Transduction
Superoxide Dismutase
/ genetics
Transplantation, Heterologous
6PGD
effector T cells
metabolism
pentose phosphate pathway
reactive oxygen species
tumor immunotherapy
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
received:
23
06
2020
revised:
07
11
2020
accepted:
16
02
2021
entrez:
10
3
2021
pubmed:
11
3
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
Although T cell expansion depends on glycolysis, T effector cell differentiation requires signaling via the production of reactive oxygen species (ROS). Because the pentose phosphate pathway (PPP) regulates ROS by generating nicotinamide adenine dinucleotide phosphate (NADPH), we examined how PPP blockade affects T cell differentiation and function. Here, we show that genetic ablation or pharmacologic inhibition of the PPP enzyme 6-phosphogluconate dehydrogenase (6PGD) in the oxidative PPP results in the generation of superior CD8
Identifiants
pubmed: 33691103
pii: S2211-1247(21)00145-5
doi: 10.1016/j.celrep.2021.108831
pmc: PMC8051863
mid: NIHMS1683105
pii:
doi:
Substances chimiques
Reactive Oxygen Species
0
6-Aminonicotinamide
329-89-5
Phosphogluconate Dehydrogenase
EC 1.1.1.43
Superoxide Dismutase
EC 1.15.1.1
superoxide dismutase 2
EC 1.15.1.1
Granzymes
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108831Subventions
Organisme : NCI NIH HHS
ID : R01 CA226776
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA169470
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA238263
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK097215
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA212605
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA177558
Pays : United States
Informations de copyright
Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests V.A.B. has patents on the PD-1 pathway licensed by Bristol-Myers Squibb, Roche, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, and Dako. The authors declare no other competing interests.
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