Harnessing histone deacetylase inhibitors for enhanced cancer immunotherapy

Many cancers are capable of hindering the immune response against tumor cells, promoting their growth and spread; this has inspired research aimed at reversing these processes to reactivate the immune system, resulting in significant therapeutic advantages. One of the strategies being explored involves histone deacetylase (HDAC) inhibitors (HDACis), which represent a new category of targeted therapies that alter the immune system's reaction to cancer via epigenetic changes. Recently, six HDACis have been authorized for clinical applications. This review aims to provide a concise overview of how different classes of HDACis affect the immune system, based on both in vitro, in vivo, and clinical studies, and explore the latest advancements in combining new immunotherapies with these drugs. HDACis have been found to influence how various cancer treatments work by, for instance, enhancing access to exposed DNA through the relaxation of chromatin, disrupting DNA repair mechanisms, and boosting the expression of immune checkpoint receptors. Combining HDACis with immunotherapy could enhance antitumor effects and reduce drug resistance.