Methylation of immune synapse genes modulates tumor immunogenicity
Methylation of immune synapse genes modulates tumor immunogenicity
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DOI：
10.1172/jci131234
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发表时间：
2020-02-03
影响因子：
15.9
通讯作者：
Kim, Sungjune
中科院分区：
文献类型：
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作者：
Berglund, Anders;Mills, Matthew;Kim, Sungjune
癌症免疫逃避是通过免疫编辑、免疫原性免疫细胞募集、免疫抑制因子分泌等多层免疫耐受机制实现的。最近免疫检查点抑制剂在癌症免疫治疗中的成功表明，功能失调的免疫突触是一个关键的耐受性机制。肿瘤细胞通过表达免疫突触蛋白来抑制免疫系统，这通常受表观遗传机制的调节。当关键免疫突触基因的甲基化状态被询问时，我们观察到不成比例的高甲基化共刺激基因和低甲基化免疫检查点基因，它们与功能性T细胞募集到肿瘤微环境负相关。因此，免疫突触基因的甲基化状态反映了肿瘤的免疫原性，并与生存相关。
Cancer immune evasion is achieved through multiple layers of immune tolerance mechanisms including immune editing, recruitment of tolerogenic immune cells, and secretion of immunosuppressive cytokines. Recent success with immune checkpoint inhibitors in cancer immunotherapy suggests a dysfunctional immune synapse as a pivotal tolerogenic mechanism. Tumor cells express immune synapse proteins to suppress the immune system, which is often modulated by epigenetic mechanisms. When the methylation status of key immune synapse genes was interrogated, we observed disproportionately hypermethylated costimulatory genes and hypomethylation of immune checkpoint genes, which were negatively associated with functional T cell recruitment to the tumor microenvironment. Therefore, the methylation status of immune synapse genes reflects tumor immunogenicity and correlates with survival.