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 2

Identification of new TAM subpopulations in GBM.

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Identification of new TAM subpopulations in GBM. The understanding of TA...
The understanding of TAM heterogeneity and functional plasticity in the GBM TME is expanding with the development of single-cell technologies (e.g., scRNA-Seq and CyTOF). Unbiased pathway analyses followed by functional validations would help characterize context-dependent TAM functions. Notably, quite a few TAM subpopulations and their potential biological functions have been identified and deciphered (as indicated). CD73, cluster of differentiation 73; CyTOF, cytometry by time of flight; GBM, glioblastoma; HGG-AM, high-grade glioma–associated microglia; HMOX1, heme oxygenase 1; MARCO, macrophage receptor with collagenous structure; scRNA-Seq, single-cell RNA sequencing; TAM, tumor-associated macrophage; TME, tumor microenvironment.