Epigenetic therapy in immune-oncology

Abstract

DNA methylation inhibitors have become the mainstay for treatment of certain haematological malignancies. In addition to their abilities to reactivate genes, including tumour suppressors, that have acquired DNA methylation during carcinogenesis, they induce the expression of thousands of transposable elements including endogenous retroviruses and latent cancer testis antigens normally silenced by DNA methylation in most somatic cells. This results in a state of viral mimicry in which treated cells mount an innate immune response by turning on viral defence genes and potentially expressing neoantigens. Furthermore, these changes mediated by DNA methylation inhibitors can also alter the function of immune cells relevant to acquired immunity. Additionally, other inhibitors of epigenetic processes, such as histone deacetylases, methylases and demethylases, can elicit similar effects either individually or in combinations with DNA methylation inhibitors. These findings together with rapid development of immunotherapies open new avenues for cancer treatment.