Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle.

Détails

ID Serval
serval:BIB_A10BFBC01F0D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Uncoupling protein 2 reprograms the tumor microenvironment to support the anti-tumor immune cycle.
Périodique
Nature immunology
Auteur(s)
Cheng W.C., Tsui Y.C., Ragusa S., Koelzer V.H., Mina M., Franco F., Läubli H., Tschumi B., Speiser D., Romero P., Zippelius A., Petrova T.V., Mertz K., Ciriello G., Ho P.C.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
02/2019
Peer-reviewed
Oui
Volume
20
Numéro
2
Pages
206-217
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: 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 <sup>+</sup> T cell-dependent anti-tumor immune cycle and normalizes the tumor vasculature. Finally we show, using either a genetic or pharmacological approach, that induction of UCP2 sensitizes melanomas to programmed cell death protein-1 blockade treatment and elicits effective anti-tumor responses. Together, this study demonstrates that targeting the UCP2 pathway is a potent strategy for alleviating the immunosuppressive TME and overcoming the primary resistance of programmed cell death protein-1 blockade.
Mots-clé
Animals, Antineoplastic Agents, Immunological/pharmacology, Antineoplastic Agents, Immunological/therapeutic use, CD8-Positive T-Lymphocytes/immunology, Cell Line, Tumor, Dendritic Cells/immunology, Drug Resistance, Neoplasm/immunology, Female, Humans, Immunotherapy/methods, Interferon Regulatory Factors/immunology, Interferon Regulatory Factors/metabolism, Melanoma, Experimental/blood supply, Melanoma, Experimental/drug therapy, Melanoma, Experimental/immunology, Melanoma, Experimental/mortality, Mice, Inbred C57BL, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Programmed Cell Death 1 Receptor/immunology, Skin Neoplasms/blood supply, Skin Neoplasms/drug therapy, Skin Neoplasms/immunology, Skin Neoplasms/mortality, Survival Analysis, Treatment Outcome, Tumor Microenvironment/immunology, Uncoupling Protein 2/genetics, Uncoupling Protein 2/immunology, Uncoupling Protein 2/metabolism
Pubmed
Web of science
Création de la notice
11/02/2019 7:54
Dernière modification de la notice
20/08/2019 15:07
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