Methylation of immune synapse genes modulates tumor immunogenicity

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Abstract

Cancer immune evasion is achieved through multiple layers of immune tolerance mechanisms including immune editing, recruitment of tolerogenic immune cells, and secretion of immune suppressive 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 hyper-methylated co-stimulatory genes and hypo-methylation 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.

Authors

Anders Berglund, Matthew Mills, Ryan M. Putney, Imène Hamaidi, James Mulé, Sungjune Kim