Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy
Fatima Khan, … , Amy B. Heimberger, Peiwen Chen
Fatima Khan, … , Amy B. Heimberger, Peiwen Chen
Published January 3, 2023
Citation Information: J Clin Invest. 2023;133(1):e163446. https://doi.org/10.1172/JCI163446.
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Review Series

Macrophages and microglia in glioblastoma: heterogeneity, plasticity, and therapy

Abstract

Glioblastoma (GBM) is the most aggressive tumor in the central nervous system and contains a highly immunosuppressive tumor microenvironment (TME). Tumor-associated macrophages and microglia (TAMs) are a dominant population of immune cells in the GBM TME that contribute to most GBM hallmarks, including immunosuppression. The understanding of TAMs in GBM has been limited by the lack of powerful tools to characterize them. However, recent progress on single-cell technologies offers an opportunity to precisely characterize TAMs at the single-cell level and identify new TAM subpopulations with specific tumor-modulatory functions in GBM. In this Review, we discuss TAM heterogeneity and plasticity in the TME and summarize current TAM-targeted therapeutic potential in GBM. We anticipate that the use of single-cell technologies followed by functional studies will accelerate the development of novel and effective TAM-targeted therapeutics for GBM patients.

Authors

Fatima Khan, Lizhi Pang, Madeline Dunterman, Maciej S. Lesniak, Amy B. Heimberger, Peiwen Chen

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Figure 1

TAM origin, identity, and heterogeneity in GBM.

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TAM origin, identity, and heterogeneity in GBM. TAMs in GBM include brai...
TAMs in GBM include brain-resident microglia and macrophages that arise from the yolk sac and bone marrow and can be characterized as CD11b+CD45lo and CD11b+CD45hi cells, respectively. In addition to specific markers, microglia can be distinguished from macrophages using advanced approaches (e.g., single-cell technologies, genetically engineered mouse models, lineage tracing, and intravital two-photon microscopy). TAM heterogeneity is regulated in a context-dependent manner (e.g., distinct tumor origins, genetic and epigenetic alterations, treatments, and sex of the host). TAMs are typically characterized as immunostimulatory (antitumor) and immunosuppressive (protumor) phenotypes. However, single-cell technology development expands our understanding of this plasticity in GBM.