4.5 Review

EZH2 inhibition: a promising strategy to prevent cancer immune editing

Journal

EPIGENOMICS
Volume 12, Issue 16, Pages 1457-1476

Publisher

FUTURE MEDICINE LTD
DOI: 10.2217/epi-2020-0186

Keywords

cancer immunotherapy; epigenetics; EZH2; immune editing

Funding

  1. Higher Education Innovation Fund (HEIF-UK)
  2. Canadian Foundation for Translational Immunology
  3. CIHR [141635, 144159, 153081]
  4. TFRI program project [1062]
  5. MITACS [IT14958]
  6. National Cancer Institute [P50CA097186]

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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.

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