Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker

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

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.


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Genome Medicine

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Published Here
August 10, 2022


Glioblastoma, Single-cell RNA-seq, Cancer immunotherapy, Macrophages