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Review
. 2023 May 12;12(10):3430.
doi: 10.3390/jcm12103430.

Immunopathology of Extracellular Vesicles in Macrophage and Glioma Cross-Talk

Timothy J Kopper  1 , Xiaoli Yu  1 , Michael W Graner  1
Affiliations
Review

Immunopathology of Extracellular Vesicles in Macrophage and Glioma Cross-Talk

Timothy J Kopper et al. J Clin Med. .

Abstract

Glioblastomas (GBM) are a devastating disease with extremely poor clinical outcomes. Resident (microglia) and infiltrating macrophages are a substantial component of the tumor environment. In GBM and other cancers, tumor-derived extracellular vesicles (EVs) suppress macrophage inflammatory responses, impairing their ability to identify and phagocytose cancerous tissues. Furthermore, these macrophages then begin to produce EVs that support tumor growth and migration. This cross-talk between macrophages/microglia and gliomas is a significant contributor to GBM pathophysiology. Here, we review the mechanisms through which GBM-derived EVs impair macrophage function, how subsequent macrophage-derived EVs support tumor growth, and the current therapeutic approaches to target GBM/macrophage EV crosstalk.

Keywords: exosomes; extracellular vesicles; glioblastoma; macrophage; microglia.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
GBM-derived EV cargo manipulates macrophages and microglia physiology towards tumor-supportive functions. EVs are released from GBM tissue and have immunosuppressive effects on nearby macrophages and microglia, promoting their conversion towards an M2-like tumor-supportive phenotype. This effect on macrophages is mediated through EV cargo, including STAT3 [49], microRNA-214-5p [52], microRNA-27a-3p [50], and potential anti-inflammatory cytokines [49]. Depicted microRNA structures are not representative of actual structure.
Figure 2
Figure 2
Macrophages and microglia exposed to GBM-derived EVs produce tumor-supportive EV cargo. These macrophages and microglia, modified by GBM EV-cargo, then release EVs that support tumor growth, migration, and chemotherapy resistance. This is mediated through EV cargo, including microRNA-124 [54,74], microRNA-27b-3p [56], microRNA-27a-3p [55], microRNA-22-3p and 221-3p [55], circularRNA-KIP18A [57], and Arginase-1 [58]. Collectively, this crosstalk suppresses the immune response to the tumor and supports further tumor growth. Depicted microRNA structures are not representative of actual structure.
See this image and copyright information in PMC

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