Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker
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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.
“Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker”
AUTHORS: Andrew X. Chen, Robyn D. Gartrell, Junfei Zhao, Pavan S. Upadhyayula, Wenting Zhao, Jinzhou Yuan, Hanna E. Minns, Athanassios Dovas, Jeffrey N. Bruce, Anna Lasorella, Antonio Iavarone, Peter Canoll, Peter A. Sims, Raul Rabadan.
LINK TO PUBLICATION:
Genome Med. 2021 May 7. doi: 10.1186/s13073-021-00906-x