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

• Published in: Genome medicine Vol. 13; no. 1; pp. 88 - 13
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.05.2021; BioMed Central; BMC
• Subjects: Biomarkers, Tumor; Bone marrow; Brain cancer; Cancer; Cancer immunotherapy; Cell Communication - genetics; Datasets; Fluorescent Antibody Technique; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - etiology; Glioblastoma - metabolism; Glioblastoma - mortality; Glioblastoma multiforme; Glioma; Growth factors; High-Throughput Nucleotide Sequencing; Humans; Immune checkpoint; Immunofluorescence; Immunohistochemistry; Immunotherapy; Isocitrate Dehydrogenase - genetics; Laboratories; Lung cancer; Lung cancer, Non-small cell; Macrophages; MARCO protein; Melanoma; Mesenchyme; Mutation; Non-small cell lung carcinoma; Patients; PD-1 protein; Population; Principal components analysis; Prognosis; Receptors, Immunologic - genetics; RNA; Scavenger receptors; Single-Cell Analysis - methods; Single-cell RNA-seq; Small cell lung carcinoma; Stem cells; Survival analysis; Therapeutic targets; Tumor markers; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumor-Associated Macrophages - metabolism; Tumor-Associated Macrophages - pathology; Cancer immunotherapy; Macrophages; Single-cell RNA-seq; Glioblastoma
• DOI: 10.1186/s13073-021-00906-x
• ISSN: 1756-994X

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.