title: Understanding the epigenetic regulation of tumours and their microenvironments: opportunities and problems for epigenetic therapy.
abstract: The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence is underscoring the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ('epimutations'), there is also a growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells towards an immunosuppressive state. Pharmacological inhibition of DNA methylation and histone modifications can augment the efficiency of immune checkpoint blockage, and unleash anti-tumour T-cell responses. However, these non-specific agents also represent a 'double-edged sword', as they can also reactivate gene transcription of checkpoint molecules, interrupting immune surveillance programmes. By understanding the impact of epigenetic control on the tumour microenvironment, rational combinatorial epigenetic and checkpoint blockage therapies have the potential to harness the immune system for the treatment of cancer. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
authors: School of Biomedical Sciences and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.
authors: Man
authors: M
authors: Liu
authors: School of Biomedical Sciences and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.
authors: Jingying
authors: J
authors: Zhou
authors: AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, PR China.
authors: Zhiwei
authors: Z
authors: Chen
authors: School of Biomedical Sciences and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, SAR, PR China.
authors: Alfred Sze-Lok
authors: AS
authors: Cheng
mesh_terms: D044127:Epigenesis, Genetic / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000235:genetics* / Q000276:immunology
keywords: DNA demethylating agents; cancer-associated fibroblast; cytotoxic T lymphocyte; dendritic cell; histone deacetylase inhibitors; macrophage; mesenchymal stem cell; microRNA; myeloid-derived suppressor cell; natural killer cell; regulatory T cell; tumour-associated antigens