Department of Bioinformatics and Biostatistics.
Department of Radiation Oncology.
J Clin Invest. 2020 Feb 3;130(2):974-980. doi: 10.1172/JCI131234.
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.
癌症的免疫逃逸是通过多层次的免疫耐受机制实现的，包括免疫编辑、耐受性免疫细胞的募集和免疫抑制性细胞因子的分泌。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种关键的耐受机制。肿瘤细胞表达免疫突触蛋白来抑制免疫系统，而这通常是由表观遗传机制调节的。当我们检测关键免疫突触基因的甲基化状态时，我们观察到共刺激基因异常高甲基化和免疫检查点基因低甲基化，这与功能性 T 细胞向肿瘤微环境的募集呈负相关。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。
