Histone deacetylase inhibitors in the generation of the anti-tumour immune response

Abstract

Acetylation of lysine residues acts to modify the function of a wide range of proteins. In histones, it affects chromatin structure, which can impact gene transcription, whereas acetylation of transcription factors and heat-shock proteins affect their activity. Deacetylase inhibitors block the dynamic turnover of acetylation resulting in hyperacetylation of target proteins. This can affect a wide range of cellular functions, and in a wide range of tumour cell types promote cytostatic and cytotoxic effects, but has little effect on normal cells. The inhibitors are being used clinically as anti-cancer agents. Although direct effects of the histone deacetylase (HDAC) inhibitors on cancers are beginning to be elucidated, the prospect of concurrent stimulation of the immune response raises hopes for immune attack of the tumour as part of the initial anti-cancer therapy and long-term immune-surveillance of residual or recurrent tumour. This review will examine the evidence for the generation of anti-tumour immunity after treatment of cancers with HDAC inhibitors.