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Review
. 2013:2013:285246.
doi: 10.1155/2013/285246. Epub 2013 Jul 24.

The controversial role of microglia in malignant gliomas

Jun Wei  1 , Konrad Gabrusiewicz, Amy Heimberger
Affiliations
Review

The controversial role of microglia in malignant gliomas

Jun Wei et al. Clin Dev Immunol. 2013.

Abstract

Malignant gliomas contain stroma and a variety of immune cells including abundant activated microglia/macrophages. Mounting evidence indicates that the glioma microenvironment converts the glioma-associated microglia/macrophages (GAMs) into glioma-supportive, immunosuppressive cells; however, GAMs can retain intrinsic anti-tumor properties. Here, we review and discuss this duality and the potential therapeutic strategies that may inhibit their glioma-supportive and propagating functions.

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Figures

Figure 1
Figure 1
Cell lineage derivation of the CNS microglia/macrophage is depicted, with arrows indicating lineage relatedness. Myeloid-derived suppressor cells (MDSCs) are a lineage term describing glioma-associated microglia/macrophages (GAMs).
Figure 2
Figure 2
CNS macrophage/monocytes differentiate into polarized macrophage subsets when exposed to different cytokine milieu. In the presence of granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-(IFN) γ, lipopolysaccharide (LPS) and other microbial products, monocytes differentiate into M1 macrophages. In the presence of macrophage colony stimulating factor (M-CSF), interleukin-(IL) 4, IL-6, IL-10 and immune suppressive molecules (corticosteroids, vitamin D3, prostaglandins), monocytes differentiate into M2 macrophages. M1 and M2 subsets differ in terms of phenotype and functions. M1 cells have high anti-microbial activity, immune stimulatory functions and tumor cytotoxicity and express the signal transducer and activator of transcription 1 (STAT-1). M2 cells have high scavenging ability, promote tissue repair and angiogenesis, favor tumor progression and express STAT-3.
Figure 3
Figure 3
Glioma-associated microglia/macrophages (GAMs) have anti-tumoral potential. In certain circumstances, GAMs can be activated and polarized to a M1-like phenotype that can contribute to both innate and adaptive anti-tumor immunity.
Figure 4
Figure 4
Glioma-associated microglia/macrophages (GAMs) are tumor supportive. Chemokines have a prominent role as they induce neoangiogenesis, activate matrix-metalloproteases (MMPs) and stroma remodeling, and direct tumor growth. Selected chemokines and immunosuppressive cytokines inhibit the anti-tumor immune response.
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