Overcoming immune suppression with epigenetic modification in ovarian cancer

Abstract

The impressive successes of immunotherapy have yet to be reliably translated to treatment of ovarian cancer, which may be a consequence of the unique barriers to T cell migration and tumor engagement in the peritoneal cavity and omentum. Epigenetic alterations contribute to establishment of these barriers and other mechanisms of immune subversion; therefore, epigenetic modifying agents represent an opportunity to mount effective antitumor immune responses by disrupting this finely tuned tumor epigenetic framework. Here, we discuss how epigenetic modifiers might permit and stimulate de novo antitumor immune responses in ovarian cancer, focusing largely on 2 common classes, DNA methyltransferase and histone deacetylase inhibitors. Specifically, increasing T and NK cell trafficking to the tumor microenvironment as well as induction of altered tumor cell phenotypes that promote immune engagement and cytotoxicity may provide a platform upon which to elaborate existing immunotherapeutic strategies. Indeed, promising combination of epigenetic modifying agents with checkpoint blockade antibodies or cellular therapies in preclinical models has led to a burgeoning number of clinical trials. Therefore, rather than implementation as a monotherapy, epigenetic modifiers may well be best suited as adjuvants in combinatorial strategies, potentiating antitumor immune responses and unleashing the promise of immunotherapy in ovarian cancer.