Language

English

Publication Date

3-28-2023

Journal

Cell Reports

DOI

10.1016/j.celrep.2023.112197

PMID

36871221

Abstract

Recent studies have shown the importance of the dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression in glioma; however, it is still unclear if myeloid cells play a role in low-grade glioma (LGG) malignant progression. Here, we investigate the cellular heterogeneity of the TME using single-cell RNA sequencing in a murine glioma model that recapitulates the malignant progression of LGG to HGG. LGGs show increased infiltrating CD4+ and CD8+ T cells and natural killer (NK) cells in the TME, whereas HGGs abrogate this infiltration. Our study identifies distinct macrophage clusters in the TME that show an immune-activated phenotype in LGG but then evolve to an immunosuppressive state in HGG. We identify CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Targeting these intra-tumoral macrophages in the LGG stage may attenuate their immunosuppressive properties and impair malignant progression.

Keywords

Mice, Animals, Brain Neoplasms, CD8-Positive T-Lymphocytes, Disease Models, Animal, Glioma, Macrophages, Sequence Analysis, RNA, Tumor Microenvironment, CD74. CP: Cancer. CP: Neuroscience. MHCII. glioblastoma. immunosuppressive TME. low-grade glioma. malignant progression. myeloid cells. single-cell RNA sequencing

Published Open-Access

yes

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