Overcoming Immune Checkpoint Blockade Resistance via EZH2 Inhibition

Hye-Jung Kim; Harvey Cantor; Kat Cosmopoulos

doi:10.1016/j.it.2020.08.010

Overcoming Immune Checkpoint Blockade Resistance via EZH2 Inhibition

Trends Immunol. 2020 Oct;41(10):948-963. doi: 10.1016/j.it.2020.08.010.

Authors

Hye-Jung Kim¹, Harvey Cantor¹, Kat Cosmopoulos²

Affiliations

¹ Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02115, USA.
² Epizyme, Inc., Cambridge, MA 02139, USA. Electronic address: KCosmopoulos@epizyme.com.

PMID: 32976740
DOI: 10.1016/j.it.2020.08.010

Abstract

Recent progress in cancer immunotherapy highlights the power of the immune system to control tumors, although a small patient subset responds to current immunotherapies. Additional approaches to mobilize antitumor immunity are required to overcome primary and acquired resistance to immunotherapy such as immune checkpoint blockade (ICB). Emerging evidence shows that targeting epigenetic elements that promote tumor progression and inhibit immune cell activity can enhance antitumor immunity by reshaping the tumor microenvironment (TME). Here, we review the pleiotropic functions in tumor and immune cells of enhancer of zeste homolog 2 (EZH2), the catalytic subunit of polycomb repressive complex 2 (PRC2), with a focus on EZH2 inhibition as a potentially promising approach to enhance current immunotherapies and improve patient outcomes for certain cancers.

Keywords: EZH2; immunotherapy; tumor microenvironment.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Enhancer of Zeste Homolog 2 Protein* / antagonists & inhibitors
Humans
Immune Checkpoint Inhibitors / therapeutic use
Immunotherapy*
Neoplasms* / drug therapy
Tumor Microenvironment* / immunology

Substances

Immune Checkpoint Inhibitors
Enhancer of Zeste Homolog 2 Protein