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 3

Current TAM-targeted therapeutic approaches in GBM.

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Current TAM-targeted therapeutic approaches in GBM. Depending on the wor...
Depending on the working mechanisms, strategies for targeting TAMs include (a) targeting TAM recruitment; (b) targeting TAM immunosuppressive reprogramming; (c) targeting new TAM subpopulations; and (d) targeting TAM-mediated phagocytosis. The key targets and associated drug candidates are indicated. 4-1BB, TNF receptor superfamily member 9; AHR, aryl hydrocarbon receptor; BACE1, β-site amyloid precursor protein–cleaving enzyme 1; BAPN, β-aminopropionitrile; CCR2, C-C motif chemokine receptor 2; CHI3L1, chitinase-3–like 1; CLOCK, circadian locomotor output cycles protein kaput; CSF-1, colony-stimulating factor 1; CSF-1R, CSF-1 receptor; GAL3, galectin-3; Gal3BP, galectin-3–binding protein; HMOX1, heme oxygenase 1; Kyn, kynurenine; LGMN, legumain; LOX, lysyl oxidase; MAGL, monoacylglycerol lipase; MARCO, macrophage receptor with collagenous structure; OLFML3, olfactomedin-like 3; OPN, osteopontin; PGE2, prostaglandin E2; PSGL-1, P-selectin glycoprotein ligand-1; ROBO1/2, roundabout receptor 1/2; SELP, P-selectin; SIRPα, signal-regulatory protein-α; SLIT2, slit guidance ligand 2; TβRI, TGF-β receptor type I.