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Review
. 2018 Feb 21;9(29):20908-20927.
doi: 10.18632/oncotarget.24556. eCollection 2018 Apr 17.

Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages

Amber E de Groot  1   2 , Kenneth J Pienta  1   2   3   4
Affiliations
Review

Epigenetic control of macrophage polarization: implications for targeting tumor-associated macrophages

Amber E de Groot et al. Oncotarget. .

Abstract

The progression of cancer is a result of not only the growth of the malignant cells but also the behavior of other components of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are key components of the TME that influence tumor growth and disease progression. TAMs can either inhibit or support tumor growth depending on their polarization to classically-activated macrophages (M1s) or alternatively-activated macrophages (M2s), respectively. Epigenetic regulation plays a significant role in determining this polarization and manipulating the epigenetic regulation in macrophages would provide a means for selectively targeting M2s thereby eliminating tumor-supporting TAMs while sparing tumor-inhibiting M1 TAMs. Many pharmacologic modulators of epigenetic enzymes are currently used clinically and could be repurposed for treating tumors with high TAM infiltrate. While much research involving epigenetic enzymes and their modulators has been performed in M1s, significantly less is known about the epigenetic regulation of M2s. This review highlights the field's current knowledge of key epigenetic enzymes and their pharmacologic modulators known to influence macrophage polarization.

Keywords: epigenetics; macrophage; macrophage polarization; tumor microenvironment; tumor-associated macrophage.

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Conflict of interest statement

CONFLICTS OF INTEREST The authors have no conflicts to declare.

Figures

Figure 1
Figure 1. Epigenetic enzymes control macrophage phenotype
Epigenetic enzymes known to control (A) DNA methylation, (B) histone methylation, and (C) histone acetylation in macrophages are listed above the left side of the spectrum if they promote M1 polarization and below if they inhibit M1 polarization. Those known to control M2 polarization are listed likewise on the right side of the spectrum.
Figure 2
Figure 2. Pharmacologic modulators of epigenetic enzymes influence macrophage phenotype
Pharmacologic modulators known to influence (A) DNA methylation, (B) histone methylation, and (C) histone acetylation in macrophages are listed above the left side of the spectrum if they promote M1 polarization and below if they inhibit M1 polarization. Those known to control M2 polarization are listed likewise on the right side of the spectrum.
See this image and copyright information in PMC

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