异常的DNA甲基化是肿瘤表观遗传特征的基本描述。我们在这里展示，畸变的DNA甲基化可以调节16种癌症类型的肿瘤免疫微环境。启动子区域的差异性DNA甲基化可以调节与免疫相关基因的转录组模式，而DNA去甲基化主要参与免疫、癌变和免疫浸润过程。此外，许多癌症类型都具有激活先天免疫应答、γ干扰素应答和NOD样受体信号通路等免疫相关功能。DNA甲基化可以进一步帮助识别肾透明细胞癌的分子亚型。这些亚型以DNA甲基化模式、主要组织相容性复合物、细胞溶解活性和细胞毒性T淋巴细胞以及肿瘤突变负荷为特征，而具有去甲基化模式的亚型则显示出不稳定的免疫状态。然后，我们调查了疲劳相关标记基因的DNA甲基化模式，并进一步展示了去甲基化在肿瘤免疫微环境中的作用。总之，我们的研究结果支持使用去甲基化作为生物标志物以了解肿瘤免疫环境的机制。

Abnormal DNA methylation is a fundamental characterization of epigenetics in cancer. Here we demonstrate that aberrant DNA methylating can modulate the tumour immune microenvironment in 16 cancer types. Differential DNA methylation in promoter region can regulate the transcriptomic pattern of immune-related genes and DNA hypomethylation mainly participated in the processes of immunity, carcinogenesis and immune infiltration. Moreover, many cancer types shared immune-related functions, like activation of innate immune response, interferon gamma response and NOD-like receptor signalling pathway. DNA methylation can further help identify molecular subtypes of kidney renal clear cell carcinoma. These subtypes are characterized by DNA methylation pattern, major histocompatibility complex, cytolytic activity and cytotoxic t lymphocyte and tumour mutation burden, and subtype with hypomethylation pattern shows unstable immune status. Then, we investigate the DNA methylation pattern of exhaustion-related marker genes and further demonstrate the role of hypomethylation in tumour immune microenvironment. In summary, our findings support the use of hypomethylation as a biomarker to understand the mechanism of tumour immune environment.