Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors

Immunotherapy. 2016 Jun;8(6):705-19. doi: 10.2217/imt-2016-0014.

Abstract

Immune surveillance should be directed to suppress tumor development and progression, involving a balance of coinhibitory and costimulatory signals that amplify immune response without overwhelming the host. Immunotherapy confers durable clinical benefit in 'immunogenic tumors', whereas in other tumors the responses are modest. Thus, immune checkpoint inhibitors may need to be combined with strategies to boost immune response or increase the tumor immune profile. Epigenetic aberrations contribute significantly to carcinogenesis. Recent findings suggest that epigenetic drugs prime the immune response by increasing expression of tumor-associated antigens and immune-related genes, as well as modulating chemokines and cytokines involved in immune system activation. This review describes our current understanding regarding epigenetic and immunotherapy combination, focusing on immune response priming to checkpoint blockade.

Keywords: DNMT inhibitor; HDAC inhibitor; cancer; checkpoint inhibitors; epigenetics; immunotherapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • CD8-Positive T-Lymphocytes / immunology*
  • Combined Modality Therapy
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors
  • Epigenesis, Genetic*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunologic Surveillance
  • Immunotherapy / methods*
  • Lymphocyte Activation
  • Neoplasms / immunology
  • Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • Costimulatory and Inhibitory T-Cell Receptors
  • Immunologic Factors