Thioredoxin-1 improves the immunometabolic phenotype of antitumor T cells.
Animals
Antioxidants
/ metabolism
Cell Line, Tumor
Glucose Transporter Type 1
/ metabolism
L-Selectin
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria
/ metabolism
Oxidative Stress
Phenotype
Reactive Oxygen Species
/ metabolism
Receptors, Antigen, T-Cell
/ metabolism
Recombinant Proteins
/ biosynthesis
T-Lymphocytes
/ cytology
Thioredoxins
/ genetics
Tumor Microenvironment
gp100 Melanoma Antigen
/ genetics
T-cell
adoptive cell therapy
antioxidant
cell metabolism
cell-surface thiol
immunotherapy
melanoma
redox protein
thioredoxin
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
07 06 2019
07 06 2019
Historique:
received:
16
11
2018
revised:
25
03
2019
pubmed:
12
4
2019
medline:
26
2
2020
entrez:
12
4
2019
Statut:
ppublish
Résumé
Adoptive transfer of tumor epitope-reactive T cells has emerged as a promising strategy to control tumor growth. However, chronically-stimulated T cells expanded for adoptive cell transfer are susceptible to cell death in an oxidative tumor microenvironment. Because oxidation of cell-surface thiols also alters protein functionality, we hypothesized that increasing the levels of thioredoxin (Trx), an antioxidant molecule facilitating reduction of proteins through cysteine thiol-disulfide exchange, in T cells will promote their sustained antitumor function. Using pre-melanosome protein (Pmel)-Trx1 transgenic mouse-derived splenic T cells, flow cytometry, and gene expression analysis, we observed here that higher Trx expression inversely correlated with reactive oxygen species and susceptibility to T-cell receptor restimulation or oxidation-mediated cell death. These Trx1-overexpressing T cells exhibited a cluster of differentiation 62L
Identifiants
pubmed: 30971427
pii: S0021-9258(20)35166-8
doi: 10.1074/jbc.RA118.006753
pmc: PMC6556575
doi:
Substances chimiques
Antioxidants
0
Glucose Transporter Type 1
0
Pmel protein, mouse
0
Reactive Oxygen Species
0
Receptors, Antigen, T-Cell
0
Recombinant Proteins
0
gp100 Melanoma Antigen
0
L-Selectin
126880-86-2
Thioredoxins
52500-60-4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
9198-9212Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008716
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA154778
Pays : United States
Organisme : NIH HHS
ID : S10 OD010731
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001450
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA137725
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA138930
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138313
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103542
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA198646
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA203628
Pays : United States
Informations de copyright
© 2019 Chakraborty et al.
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