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Review
. 2019 Nov 6;104(3):442-449.
doi: 10.1016/j.neuron.2019.08.028.

Microglia/Brain Macrophages as Central Drivers of Brain Tumor Pathobiology

David H Gutmann  1 , Helmut Kettenmann  2
Affiliations
Review

Microglia/Brain Macrophages as Central Drivers of Brain Tumor Pathobiology

David H Gutmann et al. Neuron. .

Abstract

One of the most common brain tumors in children and adults is glioma or astrocytoma. There are few effective therapies for these cancers, and patients with malignant glioma fare poorly, even after aggressive surgery, chemotherapy, and radiation. Over the past decade, it is now appreciated that these tumors are composed of numerous distinct neoplastic and non-neoplastic cell populations, which could each influence overall tumor biology and response to therapy. Among these noncancerous cell types, monocytes (microglia and macrophages) predominate. In this Review, we discuss the complex interactions involving microglia and macrophages relevant to glioma formation, progression, and response to therapy.

Keywords: glioblastoma; glioma; immune; macrophages; microglia; monocyte.

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Figures

Figure 1.
Figure 1.. GAM increase glioma growth through the release of mitogens and invasion promoting factors.
Brain microglia and infiltrating peripheral macrophages (GAM) become reprogrammed to produce growth factors that increase glioma cell proliferation, attenuate glioma cell apoptosis, and promote tumor cell migration. In this fashion, GAM produce factors that enhance (IL-10, IL-6, IL-1, EGF, and CCL5) through binding to their cognate receptors (right). In addition, SPP1 has been reported to both increase (“+”) and inhibit (“−“) glioma cell growth. Moreover, GAM elaborate other factors that increase extracellular matrix (ECM) degradation and directly promote glioma cell invasion and motility (left).
Figure 2.
Figure 2.. Glioma cells recruit and reprogram GAM through the elaboration of chemokines and other soluble factors.
Chemokines produced by glioma cells actively recruit resident microglia from the brain, as well as macrophages from the blood, through binding to their cognate receptors on GAM (right). In addition, glioma cells produce proteins that increase cytokine release (EGF, Let7, and Tenascin-C; TNC), phagocytosis (ATP), and matrix metalloprotease (MMP9, MMP14) expression (versican) (left).
Figure 3.
Figure 3.. Microglia are reprogrammed by numerous cell types and conditions in the context of glioma.
As highly adaptive cells, GAM gene expression and function can be changed by glioma treatment (chemotherapy, radiation therapy), environmental stresses (hypoxia), interactions with other non-neoplastic cell types (e.g., astrocytes), and signals from the glioma cells themselves. Each of these modifications could alter the properties of GAM in ways that either promote or inhibit continued tumor growth or invasion.
See this image and copyright information in PMC

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