Methylation of immune synapse genes modulates tumor immunogenicity

被引：35

作者：

Berglund, Anders ^{[1
]}

Mills, Matthew ^{[2
]}

Putney, Ryan M. ^{[1
]}

Hamaidi, Imene ^{[3
]}

Mule, James ^{[2
,3
,4
]}

Kim, Sungjune ^{[2
,3
]}

机构：

[1] H Lee Moffitt Canc Ctr & Res Inst, Dept Bioinformat & Biostat, Tampa, FL USA

[2] H Lee Moffitt Canc Ctr & Res Inst, Dept Radiat Oncol, Tampa, FL USA

[3] H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL USA

[4] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2020年 / 130卷 / 02期

关键词：

DNA METHYLATION; EXPRESSION; CANCER; CELLS;

D O I：

10.1172/JCI131234

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：974 / 980

页数：7

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