Background Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and methods We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described. Results Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T-cell therapy, can be envisioned. Dedicated clinically relevant approaches for patient selection and trial design will be required to optimally develop such combinations. Conclusion In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.

中文翻译：

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表观遗传修饰剂是实体瘤中的新的免疫调节疗法。

背景技术在过去的几年中，免疫疗法通过改善整体生存率，彻底改变了癌症治疗方法。但是，大多数患者仍然对此类疗法有主要或次要抗性，因此提高对免疫疗法的敏感性对于改善患者预后至关重要。最近的一些证据表明，表观遗传修饰剂具有内在的免疫调节特性，这可能具有治疗意义。材料和方法我们回顾了描述或利用表观遗传因子的免疫调节特性的临床前证据和临床研究。描述了实验方法，临床适用性和相应的正在进行的临床试验。结果几种表观遗传修饰剂，例如组蛋白脱乙酰基酶抑制剂，DNA甲基转移酶抑制剂，溴结构域抑制剂，赖氨酸特异性组蛋白脱甲基酶1抑制剂和zeste homolog 2抑制剂的增强剂具有内在的免疫调节特性。后者可以通过这些药物对癌细胞（例如新抗原的呈递和产生，诱导免疫原性细胞死亡，细胞因子分泌的调节），对免疫细胞（例如线性，分化，活化状态和抗肿瘤能力）的作用来实现。或微环境的组成部分（例如调节性T细胞和巨噬细胞）。可以设想几种有希望的组合，特别是与免疫检查点阻滞剂或过继性T细胞疗法的组合。需要患者选择和试验设计的专用临床相关方法，以最佳地开发此类组合。结论在免疫疗法已成为许多肿瘤类型的治疗骨干的时代，表观遗传修饰剂可能在调节肿瘤的免疫原性和对免疫试剂的敏感性方面起着至关重要的作用。最佳的试验设计（包括机会试验窗口）将是该方法成功的关键，并且临床评估仍在进行中。