The multilayered control of acetylation during adenovirus-based immunotherapy of cancer.

Adenoviruses are highly immunogenic agents that have shown promise first as gene delivery vectors and later as oncolytic viruses. Currently, oncolytic adenoviruses are featured in over 30% of cancer virotherapy clinical trials. Due to their effective cellular uptake and hijack of cellular machinery, replication-competent adenoviruses are promising therapeutic agents for treating a wide range of tumors. Adenoviral influence on host cell acetylome regulation has regained attention, as these viruses redirect or suppress acetylation during replication, making them potentially desirable therapeutic agents for cancers driven by epigenetic modifications. In this review, we aim to cover the viral processes influencing the acetylome of the host genome. In addition, we shall discuss the effect of differential acetylation on the antiviral defense mounted by the host immune system. Lastly, we will discuss the opportunities for combining acetylation modifiers with oncolytic adenoviruses to improve further outcomes for patients treated with viroimmunotherapy.