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.
Abbreviations:
OVCA (ovarian cancer), Treg (regulatory T cell), MDSC (myeloid derived suppressor cell), DNMT (DNA methyltransferase), HDAC (histone deacetylase inhibitor), AZA (5-azacytidine), IFN (interferon), ENT (entinostat), GIV (givinostat), DAC (decitabine), TME (tumor microenvironment), MHC (major histocompatibility complex), CTA (cancer testis antigen), GUA (guadecitabine), DC (dendritic cell), DR4 (death receptor 4), CIITA (class II transcriptional activator), ERV (endogenous retrovirus), ISRE (interferon-stimulated response elements)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: June 23, 2018
Accepted:
June 18,
2018
Received in revised form:
June 12,
2018
Received:
June 6,
2018
Identification
Copyright
Published by Elsevier Inc.
