Improving cancer immunotherapy with DNA methyltransferase inhibitors

Cancer Immunol Immunother. 2016 Jul;65(7):787-96. doi: 10.1007/s00262-015-1776-3. Epub 2015 Dec 8.

Abstract

Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity.

Keywords: CITIM 2015; DNA methyltransferase inhibitor; Decitabine; Epigenetic modifier; Immunotherapy; Ovarian cancer.

Publication types

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

MeSH terms

  • Animals
  • DNA Methylation / drug effects
  • DNA Methylation / immunology
  • DNA Modification Methylases / antagonists & inhibitors*
  • DNA Modification Methylases / immunology
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / therapy*

Substances

  • Enzyme Inhibitors
  • DNA Modification Methylases