Histone Deacetylase Inhibitors as Immunomodulators in Cancer Therapeutics

Epigenomics. 2016 Mar;8(3):415-28. doi: 10.2217/epi.15.118. Epub 2016 Mar 7.

Abstract

HDAC inhibitors (HDACIs) are anticancer agents being developed in preclinical and clinical settings due to their capacity to modulate gene expression involved in cell growth, differentiation and apoptosis, through modification of both chromatin histone and nonhistone proteins. Most HDACIs in clinical development have cytotoxic or cytostatic properties and their direct inhibitory effects on tumor cells are well documented. Numerous studies have revealed that HDACIs have potent immunomodulatory activity in tumor-bearing animals and cancer patients, providing guidance to apply these agents in cancer immunotherapies. Here, we summarize recent reports addressing the effects of HDACIs on tumor cell immunogenicity, and on different components of the host immune system. In addition, we discuss the complexity of the immunomodulatory activity of these agents, which depends on the class specificity of the HDACIs, different experimental settings and the target immune cell populations.

Keywords: Foxp3; Tregs; antigen-presenting cells; cancer immunotherapy; histone deacetylase inhibitor; immunomodulation; inflammatory cytokines; myeloid-derived suppressor cells; tumor associated macrophage.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cancer Vaccines / pharmacology
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Immunologic Factors / pharmacology*
  • Immunotherapy / methods*
  • Lymphocytes / drug effects
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Oncolytic Virotherapy / methods
  • T-Lymphocytes, Regulatory / drug effects

Substances

  • Antineoplastic Agents
  • Cancer Vaccines
  • Histone Deacetylase Inhibitors
  • Immunologic Factors