Metabolism drives macrophage heterogeneity in the tumor microenvironment.
CP: Cancer
CP: Metabolism
cancer
checkpoint
immunosuppression
immunotherapy
liver
macrophage
metabolism
purine
single-cell RNA sequencing
tumor microenvironment
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
05 04 2022
05 04 2022
Historique:
received:
25
05
2021
revised:
04
01
2022
accepted:
11
03
2022
entrez:
6
4
2022
pubmed:
7
4
2022
medline:
9
4
2022
Statut:
ppublish
Résumé
Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment (TME). However, the relationship between the phenotype and metabolic pattern of TAMs remains poorly understood. We performed single-cell transcriptome profiling on hepatic TAMs from mice bearing liver metastatic tumors. We find that TAMs manifest high heterogeneity at the levels of transcription, development, metabolism, and function. Integrative analyses and validation experiments indicate that increased purine metabolism is a feature of TAMs with pro-tumor and terminal differentiation phenotypes. Like mouse TAMs, human TAMs are highly heterogeneous. Human TAMs with increased purine metabolism exhibit a pro-tumor phenotype and correlate with poor therapeutic efficacy to immune checkpoint blockade. Altogether, our work demonstrates that TAMs are developmentally, metabolically, and functionally heterogeneous and purine metabolism may be a key metabolic feature of a pro-tumor macrophage population.
Identifiants
pubmed: 35385733
pii: S2211-1247(22)00357-6
doi: 10.1016/j.celrep.2022.110609
pmc: PMC9052943
mid: NIHMS1795987
pii:
doi:
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
110609Subventions
Organisme : NCI NIH HHS
ID : P50 CA186786
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA211016
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248430
Pays : United States
Informations de copyright
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests We declare that we have no competing interests.
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