The functions of EZH2 in immune cells: Principles for novel immunotherapies

J Leukoc Biol. 2021 Jul;110(1):77-87. doi: 10.1002/JLB.1RU0520-311R. Epub 2020 Oct 11.

Abstract

Enhancer of zeste homolog 2 (EZH2) is aberrantly expressed or mutated in multiple types of cancer cells and plays an oncogenic role in tumorigenesis and development in most cancers. Results from pilot clinical studies have implied that EZH2 inhibitors have therapeutic potential against some cancers. However, the exact mechanisms by which EZH2 plays oncogenic roles and EZH2 inhibition exerts anticancer effects are incompletely understood. To date, the findings of studies focusing on EZH2 and cancer cells have failed to fully explain the observations in preclinical and clinical studies. Therefore, recent studies about the roles of EZH2 in cancers have shifted from cancer cells to immune cells. The human immune system is a complex network comprising multiple subpopulations of immune cells. Immune cells communicate and interact with cancer cells during cancer development and treatment, dictating the fate of cancer cells. Elucidating the roles of EZH2 in immune cells, especially in cancer patients, promises the identification of novel immunotherapeutic strategies or priming of existing immunotherapies against cancer. Hence, we reviewed the studies focusing on the involvement of EZH2 in various immune cells, aiming to provide ideas for immunotherapies targeting EZH2 in immune cells.

Keywords: EZH2; T cell differentiation; T cell proliferation; tumor immunity; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Disease Management
  • Disease Susceptibility
  • Enhancer of Zeste Homolog 2 Protein / genetics*
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Humans
  • Immune System / diagnostic imaging
  • Immune System / immunology
  • Immune System / metabolism
  • Immunomodulation / genetics*
  • Immunotherapy / methods
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

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