Oncolytic Viruses Engineered to Enforce Leptin Expression Reprogram Tumor-Infiltrating T Cell Metabolism and Promote Tumor Clearance.
cancer
immunometabolism
immunotherapy
leptin
memory
oncolytic virus
single cell
Journal
Immunity
ISSN: 1097-4180
Titre abrégé: Immunity
Pays: United States
ID NLM: 9432918
Informations de publication
Date de publication:
17 09 2019
17 09 2019
Historique:
received:
19
10
2018
revised:
16
05
2019
accepted:
12
07
2019
pubmed:
1
9
2019
medline:
18
12
2019
entrez:
1
9
2019
Statut:
ppublish
Résumé
Immunotherapy can reinvigorate dormant responses to cancer, but response rates remain low. Oncolytic viruses, which replicate in cancer cells, induce tumor lysis and immune priming, but their immune consequences are unclear. We profiled the infiltrate of aggressive melanomas induced by oncolytic Vaccinia virus using RNA sequencing and found substantial remodeling of the tumor microenvironment, dominated by effector T cell influx. However, responses to oncolytic viruses were incomplete due to metabolic insufficiencies induced by the tumor microenvironment. We identified the adipokine leptin as a potent metabolic reprogramming agent that supported antitumor responses. Leptin metabolically reprogrammed T cells in vitro, and melanoma cells expressing leptin were immunologically controlled in mice. Engineering oncolytic viruses to express leptin in tumor cells induced complete responses in tumor-bearing mice and supported memory development in the tumor infiltrate. Thus, leptin can provide metabolic support to tumor immunity, and oncolytic viruses represent a platform to deliver metabolic therapy.
Identifiants
pubmed: 31471106
pii: S1074-7613(19)30319-X
doi: 10.1016/j.immuni.2019.07.003
pmc: PMC6903394
mid: NIHMS1535730
pii:
doi:
Substances chimiques
Leptin
0
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
548-560.e4Subventions
Organisme : NIAID NIH HHS
ID : DP2 AI136598
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA047904
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA121973
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097190
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI135367
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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