{"title":"Epigenetic regulators combined with tumour immunotherapy: current status and perspectives.","authors":"Huan Zhang, Yutong Pang, Ling Yi, Xiaojue Wang, Panjian Wei, Haichao Wang, Shuye Lin","doi":"10.1186/s13148-025-01856-6","DOIUrl":null,"url":null,"abstract":"<p><p>Immunotherapy, particularly immune checkpoint inhibitor therapy, has demonstrated clinical benefits in solid tumours. Despite its satisfactory clinical efficacy, it still faces several issues, such as limited eligibility, low response rates and cytotoxicity. Cancer epigenetics implies that tumour cells exhibit unique phenotypes because of their unique characteristics, thus reprogramming of the epigenome holds promise for cancer therapy. Epigenetic regulation plays an important role in regulating gene expression during tumour development and maintenance. Epigenetic regulators induce cancer cell cycle arrest, apoptosis and differentiation of cancer cells, thereby exerting anti-tumour effects. Recent studies have revealed a significant correlation between epigenetic regulatory factors and immune checkpoint therapy. Epigenetics can modulate various aspects of the tumour immune microenvironment and immune response to enhance the sensitivity of immunotherapy, such as lowering the concentration required and mitigating cytotoxicity. This review primarily discusses DNA methyltransferase inhibitors, histone deacetylase inhibitors, enhancer of zeste homolog 2 inhibitors and lysine-specific demethylase 1 inhibitors, which are associated with transcriptional repression. This repression alters the expression of genes involved in the immune checkpoint, thereby enhancing the effectiveness of immunotherapy. We also discuss the potential and challenges of tumour immunotherapy and highlight its advantages, application challenges and clinical research on integrating epigenetic regulatory factors with tumour immunotherapy.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"51"},"PeriodicalIF":4.8000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11929245/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epigenetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13148-025-01856-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Immunotherapy, particularly immune checkpoint inhibitor therapy, has demonstrated clinical benefits in solid tumours. Despite its satisfactory clinical efficacy, it still faces several issues, such as limited eligibility, low response rates and cytotoxicity. Cancer epigenetics implies that tumour cells exhibit unique phenotypes because of their unique characteristics, thus reprogramming of the epigenome holds promise for cancer therapy. Epigenetic regulation plays an important role in regulating gene expression during tumour development and maintenance. Epigenetic regulators induce cancer cell cycle arrest, apoptosis and differentiation of cancer cells, thereby exerting anti-tumour effects. Recent studies have revealed a significant correlation between epigenetic regulatory factors and immune checkpoint therapy. Epigenetics can modulate various aspects of the tumour immune microenvironment and immune response to enhance the sensitivity of immunotherapy, such as lowering the concentration required and mitigating cytotoxicity. This review primarily discusses DNA methyltransferase inhibitors, histone deacetylase inhibitors, enhancer of zeste homolog 2 inhibitors and lysine-specific demethylase 1 inhibitors, which are associated with transcriptional repression. This repression alters the expression of genes involved in the immune checkpoint, thereby enhancing the effectiveness of immunotherapy. We also discuss the potential and challenges of tumour immunotherapy and highlight its advantages, application challenges and clinical research on integrating epigenetic regulatory factors with tumour immunotherapy.
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.