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

Amber E. de Groot; Kenneth J. Pienta

doi:10.18632/oncotarget.24556

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

Amber E. de Groot _ and Kenneth J. Pienta

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Oncotarget. 2018; 9:20908-20927. https://doi.org/10.18632/oncotarget.24556

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Abstract

Amber E. de Groot1,2 and Kenneth J. Pienta1,2,3,4

1The James Buchanan Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA

2Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA

3Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA

4Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA

Correspondence to:

Kenneth J. Pienta, email: [email protected]

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

Received: July 21, 2017 Accepted: September 08, 2017 Epub: February 21, 2018 Published: April 17, 2018

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.

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

Abstract