Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker.
Biomarkers, Tumor
Cell Communication
/ genetics
Fluorescent Antibody Technique
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma
/ diagnosis
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
Isocitrate Dehydrogenase
/ genetics
Mutation
Prognosis
Receptors, Immunologic
/ genetics
Single-Cell Analysis
/ methods
Tumor Microenvironment
/ genetics
Tumor-Associated Macrophages
/ metabolism
Cancer immunotherapy
Glioblastoma
Macrophages
Single-cell RNA-seq
Journal
Genome medicine
ISSN: 1756-994X
Titre abrégé: Genome Med
Pays: England
ID NLM: 101475844
Informations de publication
Date de publication:
19 05 2021
19 05 2021
Historique:
received:
07
06
2020
accepted:
07
05
2021
entrez:
20
5
2021
pubmed:
21
5
2021
medline:
19
2
2022
Statut:
epublish
Résumé
Macrophages are the most common infiltrating immune cells in gliomas and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood. We combined new and previously published single-cell RNA-seq data from 98,015 single cells from a total of 66 gliomas to profile 19,331 individual macrophages. Unsupervised clustering revealed a pro-tumor subpopulation of bone marrow-derived macrophages characterized by the scavenger receptor MARCO, which is almost exclusively found in IDH1-wild-type glioblastomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis and mesenchymal subtype. Furthermore, MARCO expression is significantly altered over the course of treatment with anti-PD1 checkpoint inhibitors in a response-dependent manner, which we validate with immunofluorescence imaging. These findings illustrate a novel macrophage subpopulation that drives tumor progression in glioblastomas and suggest potential therapeutic targets to prevent their recruitment.
Sections du résumé
BACKGROUND
Macrophages are the most common infiltrating immune cells in gliomas and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood.
METHODS
We combined new and previously published single-cell RNA-seq data from 98,015 single cells from a total of 66 gliomas to profile 19,331 individual macrophages.
RESULTS
Unsupervised clustering revealed a pro-tumor subpopulation of bone marrow-derived macrophages characterized by the scavenger receptor MARCO, which is almost exclusively found in IDH1-wild-type glioblastomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis and mesenchymal subtype. Furthermore, MARCO expression is significantly altered over the course of treatment with anti-PD1 checkpoint inhibitors in a response-dependent manner, which we validate with immunofluorescence imaging.
CONCLUSIONS
These findings illustrate a novel macrophage subpopulation that drives tumor progression in glioblastomas and suggest potential therapeutic targets to prevent their recruitment.
Identifiants
pubmed: 34011400
doi: 10.1186/s13073-021-00906-x
pii: 10.1186/s13073-021-00906-x
pmc: PMC8136167
doi:
Substances chimiques
Biomarkers, Tumor
0
MARCO protein, human
0
Receptors, Immunologic
0
Isocitrate Dehydrogenase
EC 1.1.1.41
IDH1 protein, human
EC 1.1.1.42.
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
88Subventions
Organisme : NIH HHS
ID : R01 CA185486
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007367
Pays : United States
Organisme : NIH HHS
ID : U54 CA193313
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001874
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA217858
Pays : United States
Organisme : NIH HHS
ID : R01 NS103473
Pays : United States
Organisme : NIH HHS
ID : R01 CA179044
Pays : United States
Organisme : NIH HHS
ID : U54 CA209997
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS103473
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA209997
Pays : United States
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