Author:
Chen Andrew X.,Gartrell Robyn D.,Zhao Junfei,Upadhyayula Pavan S.,Zhao Wenting,Yuan Jinzhou,Minns Hanna E.,Dovas Athanassios,Bruce Jeffrey N.,Lasorella Anna,Iavarone Antonio,Canoll Peter,Sims Peter A.,Rabadan Raul
Abstract
Abstract
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.
Funder
National Institutes of Health
National Science Foundation
Stand Up To Cancer
Swim across America
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Genetics,Molecular Biology,Molecular Medicine
Cited by
72 articles.
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