EZH2 inhibition: a promising strategy to prevent cancer immune editing

Epigenomics. 2020 Aug;12(16):1457-1476. doi: 10.2217/epi-2020-0186. Epub 2020 Sep 17.

Abstract

Immunotherapies are revolutionizing the clinical management of a wide range of cancers. However, intrinsic or acquired unresponsiveness to immunotherapies does occur due to the dynamic cancer immunoediting which ultimately leads to immune escape. The evolutionarily conserved histone modifier enhancer of zeste 2 (EZH2) is aberrantly overexpressed in a number of human cancers. Accumulating studies indicate that EZH2 is a main driver of cancer cells' immunoediting and mediate immune escape through downregulating immune recognition and activation, upregulating immune checkpoints and creating an immunosuppressive tumor microenvironment. In this review, we overviewed the roles of EZH2 in cancer immunoediting, the preclinical and clinical studies of current pharmacologic EZH2 inhibitors and the prospects for EZH2 inhibitor and immunotherapy combination for cancer treatment.

Keywords: EZH2; cancer immunotherapy; epigenetics; immune editing.

Publication types

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

MeSH terms

  • Animals
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
  • Enhancer of Zeste Homolog 2 Protein / immunology
  • Epigenesis, Genetic
  • Humans
  • Immunotherapy
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Tumor Escape

Substances

  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein