Transcriptional modulation using histone deacetylase inhibitors for cancer immunotherapy

Abstract

Epigenetic processes, in addition to well-characterized genetic abnormalities, play a critical role in cancer initiation and progression. The acetylation status of histones affects levels of gene expression, and causes aberrant transcriptional repression in cancer cells. As a result, this is also implicated with unresponsiveness to immune-based therapies as well as conventional chemotherapies against cancer. To sensitize cancer cells to those therapies, histone deacetylase inhibitors (HDACi) have attracted much attention as epigenetic-modulating agents, because these compounds possess the pleiotropic effects on malignant cells such that they are more prone to differentiation, growth arrest, and apoptosis. This chapter will highlight the pleiotropic antitumor effects of HDACi when combined with antigen-specific tumor immunotherapy, and describe the potential clinical implications for the improved cancer immunotherapy.