Genetic and epigenetic strategies for advancing ovarian cancer immunotherapy

Expert Opin Biol Ther. 2019 Jun;19(6):547-560. doi: 10.1080/14712598.2019.1602605. Epub 2019 Apr 15.

Abstract

Introduction: Immuno-oncology is currently the most popular field of cancer research and development. The surge of interest in immuno-oncology stems from recent clinical approvals and successes in clinical trials with new immuno-therapeutics and parallels a global trending interest in immunology. Among the current immunotherapeutic modalities, immune checkpoint inhibitors (ICPIs) are some of the most prominent agents that strengthens the activity of our adaptive immune system, and has demonstrated success in treating different types of cancer. With significant promises in melanoma and other solid tumors, ICPIs have also been evaluated in ovarian cancer (OC). Contrary to expectations, their efficacy for treating OC is unfortunately very low.

Areas covered: In this review, immunotherapy response in OC will be evaluated in the context of disease genetics and epigenetics, with a focus on checkpoint blockade. Also, novel genetic and epigenetic therapies that show synergistic potential with current immunotherapies will be examined in detail.

Expert opinion: The low response rate of OC to current immune checkpoint therapies may be due to the highly immunosuppressive tumor microenvironment (TME) of the disease. The application of genetic and epigenetic agents can pave the way for overcoming this barrier in OC immunotherapy.

Keywords: Ovarian cancer; PD-1/PD-L1; T-cells; epigenetics; gene silencing; immune checkpoint inhibitors; tumor microenvironment.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Epigenomics*
  • Female
  • Humans
  • Immune System / metabolism
  • Immunotherapy*
  • Neoplasm Staging
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / therapy*
  • RNA Interference

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents