The emerging role of epigenetic therapeutics in immuno-oncology

The past decade has seen the emergence of immunotherapy as a prime approach to cancer treatment, revolutionizing the management of many types of cancer. Despite the promise of immunotherapy, most patients do not have a response or become resistant to treatment. Thus, identifying combinations that potentiate current immunotherapeutic approaches will be crucial. The combination of immune-checkpoint inhibition with epigenetic therapy is one such strategy that is being tested in clinical trials, encompassing a variety of cancer types. Studies have revealed key roles of epigenetic processes in regulating immune cell function and mediating antitumour immunity. These interactions make combined epigenetic therapy and immunotherapy an attractive approach to circumvent the limitations of immunotherapy alone. In this Review, we highlight the basic dynamic mechanisms underlying the synergy between immunotherapy and epigenetic therapies and detail current efforts to translate this knowledge into clinical benefit for patients. Despite promising responses in a minority of patients with cancer, considerable scope remains to improve the efficacy of both immune-checkpoint inhibitors and epigenetic drugs, with one potential strategy involving the combination of these two types of treatment. Here, the authors describe the mechanisms underlying the synergy between immune-checkpoint inhibitors and epigenetic drugs and discuss the ongoing clinical development of such combinations.