Targeting the epigenetic regulation of antitumour immunity

Aberrant epigenetic processes can influence tumour immunogenicity and immune cells involved in the response to cancer. This Review highlights how epigenetic regulators can be modulated with small-molecule drugs to promote antitumour immune responses, and discusses the opportunities and challenges for developing cancer treatment regimens that combine epigenetic therapies with immunotherapies. Dysregulation of the epigenome drives aberrant transcriptional programmes that promote cancer onset and progression. Although defective gene regulation often affects oncogenic and tumour-suppressor networks, tumour immunogenicity and immune cells involved in antitumour responses may also be affected by epigenomic alterations. This could have important implications for the development and application of both epigenetic therapies and cancer immunotherapies, and combinations thereof. Here, we review the role of key aberrant epigenetic processes - DNA methylation and post-translational modification of histones - in tumour immunogenicity, as well as the effects of epigenetic modulation on antitumour immune cell function. We emphasize opportunities for small-molecule inhibitors of epigenetic regulators to enhance antitumour immune responses, and discuss the challenges of exploiting the complex interplay between cancer epigenetics and cancer immunology to develop treatment regimens combining epigenetic therapies with immunotherapies.