OncoTargets and Therapy (Dec 2019)
DNA Methyltransferase Inhibitors: Catalysts For Antitumour Immune Responses
Abstract
Huimin Dan, Shanshan Zhang, Yongning Zhou, Quanlin Guan Gansu Province Key Laboratory of Gastrointestinal Diseases, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of ChinaCorrespondence: Quanlin GuanGansu Province Key Laboratory of Gastrointestinal Diseases, The First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of ChinaTel +8613893473086Email [email protected]: Epigenetics is a kind of heritable change that involves the unaltered DNA sequence and can have effects on gene expression. The regulatory mechanism mainly includes DNA methylation, histone modification and non-coding RNA regulation. DNA methylation is currently the most studied aspect of epigenetics. It is widely present in eukaryotic cells and is the most important epigenetic mark in the regulation of gene expression in the cell. DNA methyltransferase inhibitors (DNMTi) have been increasingly recognized in the field of cancer immunotherapy, have been approved for the treatment of acute myeloid leukaemia (AML) and are widely being used in clinical trials of cancer immunotherapies. DNMTi promote the reactivation of tumour suppressor genes, enhance tumour immunogenicity, and stimulate a variety of immune cells to secrete cytokines that exert cytotoxic effects, promote tumour cell death, including macrophages, natural killer (NK) cells and CD8+ T cells, and upregulate major histocompatibility complex (MHC) class I expression levels. Here, we mainly summarize the epigenetics related to DNMTi and their regulation of the antitumour immune response and DNMTi combined with immuno-therapeutics or histone deacetylase inhibitors to demonstrate the great development potential and clinical application value of DNMTi.Keywords: DNA methyltransferase inhibitors, histone deacetylase inhibitor, immunomodulation, immune cells, immunotherapy, DNA methylation, epigenetics
