文章：

免疫肿瘤学的表观遗传治疗

Epigenetic therapy in immune-oncology

原文发布日期：2019-02-05

DOI: 10.1038/s41568-019-0109-9

类型: Review Article

开放获取: 否

英文摘要：

DNA methylation inhibitors have become the mainstay for treatment of certain haematological malignancies. In addition to their abilities to reactivate genes, including tumour suppressors, that have acquired DNA methylation during carcinogenesis, they induce the expression of thousands of transposable elements including endogenous retroviruses and latent cancer testis antigens normally silenced by DNA methylation in most somatic cells. This results in a state of viral mimicry in which treated cells mount an innate immune response by turning on viral defence genes and potentially expressing neoantigens. Furthermore, these changes mediated by DNA methylation inhibitors can also alter the function of immune cells relevant to acquired immunity. Additionally, other inhibitors of epigenetic processes, such as histone deacetylases, methylases and demethylases, can elicit similar effects either individually or in combinations with DNA methylation inhibitors. These findings together with rapid development of immunotherapies open new avenues for cancer treatment.

摘要翻译： 

DNA甲基化抑制剂已成为某些血液恶性肿瘤的主要治疗手段。除了能够重新激活在癌变过程中发生DNA甲基化的基因（包括肿瘤抑制基因）外，这些抑制剂还能诱导数千种转座元件的表达，包括内源性逆转录病毒和潜伏的癌睾抗原——这些元件在大多数体细胞中通常因DNA甲基化而沉默。这导致一种病毒模拟状态，在此状态下，受处理的细胞通过启动病毒防御基因并潜在表达新抗原，从而引发先天免疫反应。此外，DNA甲基化抑制剂介导的这些变化还能改变与获得性免疫相关的免疫细胞功能。另外，其他表观遗传过程抑制剂（如组蛋白去乙酰化酶、甲基化酶和去甲基化酶抑制剂）单独使用或与DNA甲基化抑制剂联合使用时，也能引发类似效应。这些发现与免疫疗法的快速发展共同为癌症治疗开辟了新途径。

原文链接：

Epigenetic therapy in immune-oncology