Epigenetic Regulation and Tumor Immunotherapy

Epigenetics is the study of DNA sequence-independent heritable changes in phenotype and gene expression. Major epigenetic mechanisms include DNA methylation, histone modification, chromatin structure regulation, and non-coding RNA regulation. Emerging evidence suggested that epigenetic regulations play central roles in tumor immunosurveillance, including tumor antigen production, the interaction between tumor cells and immune cells, and T cell development, priming, activation, and exhaustion. On the other hand, tumors commonly hijack various epigenetic mechanisms to escape immune restriction. Therefore, modulating epigenetic regulators is able to normalize the impaired immunosurveillance and/or trigger antitumor immune responses. Numerous preclinical and clinical studies revealed that epigenetic agents, including DNMT inhibitor, HDAC inhibitor, EZH2 inhibitors, LSD1 inhibitors, G9a inhibitors, and BET inhibitors, have the capacity to induce anti-tumor immune responses and modulate tumor immune microenvironment. Currently, hundreds of clinical trials that combine epigenetic agents and immune checkpoint inhibitors (ICI) are ongoing, aiming to achieve synergistic effects, reduce adverse effects, and overcome intrinsic and acquired resistance. Thus, combining epigenetic therapy with immunotherapy suggests a promising new way to improve clinical outcomes.

In this Research Topic, we aim to collect Original Research and Review articles focusing on investigating epigenetic regulation of tumor immunity, identifying key epigenetic regulators of anti-tumor immune response, and developing epigenetic targeting immune therapeutics. We hope this Research Topic will lead to a better understanding of epigenetics in tumor immunity and immunotherapy and highlight the clinical significance of epigenetic drugs. Areas of interest include but are not limited to the following aspects:
• Mechanisms on epigenetic regulation of anti-tumor immunity.
• Identification of key epigenetic regulators of anti-tumor immune response.
• Development of epigenetic therapeutics in cancer immunotherapy.

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.