Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle.
Animals
Antineoplastic Agents, Immunological
/ pharmacology
CD8-Positive T-Lymphocytes
/ immunology
Cell Line, Tumor
Dendritic Cells
/ immunology
Drug Resistance, Neoplasm
/ immunology
Female
Humans
Immunotherapy
/ methods
Interferon Regulatory Factors
/ immunology
Melanoma, Experimental
/ blood supply
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Skin Neoplasms
/ blood supply
Survival Analysis
Treatment Outcome
Tumor Microenvironment
/ immunology
Uncoupling Protein 2
/ genetics
Journal
Nature immunology
ISSN: 1529-2916
Titre abrégé: Nat Immunol
Pays: United States
ID NLM: 100941354
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
15
05
2018
accepted:
21
11
2018
entrez:
22
1
2019
pubmed:
22
1
2019
medline:
7
5
2019
Statut:
ppublish
Résumé
Immune checkpoint blockade therapy has shifted the paradigm for cancer treatment. However, the majority of patients lack effective responses due to insufficient T cell infiltration in tumors. Here we show that expression of mitochondrial uncoupling protein 2 (UCP2) in tumor cells determines the immunostimulatory feature of the tumor microenvironment (TME) and is positively associated with prolonged survival. UCP2 reprograms the immune state of the TME by altering its cytokine milieu in an interferon regulatory factor 5-dependent manner. Consequently, UCP2 boosts the conventional type 1 dendritic cell- and CD8
Identifiants
pubmed: 30664764
doi: 10.1038/s41590-018-0290-0
pii: 10.1038/s41590-018-0290-0
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Interferon Regulatory Factors
0
Irf5 protein, mouse
0
Programmed Cell Death 1 Receptor
0
Ucp2 protein, mouse
0
Uncoupling Protein 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
206-217Commentaires et corrections
Type : ErratumIn