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Choi et al. Neuroimmunol Neuroinflammation 2018;5:42 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.47 Neuroinflammation

Review Open Access

It takes two: potential therapies and insights involving
microglia and macrophages in glioblastoma

John Choi, Nicholas Mai, Christopher Jackson, Zineb Belcaid, Michael Lim

Department of Neurosurgery, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.
Correspondence to: Dr. Michael Lim, Department of Neurosurgery, Johns Hopkins School of Medicine, Johns Hopkins University,
Baltimore, MD 21231, USA. E-mail: mlim3@jhmi.edu
How to cite this article: Choi J, Mai N, Jackson C, Belcaid Z, Lim M. It takes two: potential therapies and insights involving microglia
and macrophages in glioblastoma. Neuroimmunol Neuroinflammation 2018;5:42. http://dx.doi.org/10.20517/2347-8659.2018.47

Received: 7 Aug 2018 First Decision: 29 Aug 2018 Revised: 12 Sep 2018 Accepted: 12 Sep 2018 Published: 18 Oct 2018

Science Editor: Athanassios P. Kyritsis Copy Editor: Cui Yu Production Editor: Zhong-Yu Guo

Abstract
Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune
cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and
macrophages, despite a growing body of evidence that demonstrates key structural and functional differences
between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages
has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with
this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor
microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the
differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several
potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways
in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages
offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future
directions for new treatment modalities.

Keywords: Glioblastoma, cancer, immunotherapy, myeloid, microglia, macrophages, pro-tumor, anti-tumor,
immunosuppression

INTRODUCTION
The advent of immunotherapy as a viable cancer treatment option has resulted in the rapid emergence
of new therapeutic strategies, with immune checkpoint inhibitors (ICI) serving as the cornerstone for

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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