Methylation of immune synapse genes modulates tumor immunogenicity
- 3 February 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (2), 974-980
- https://doi.org/10.1172/JCI131234
Abstract
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.Funding Information
- NIH K08 (CA194273)
- NCI Cancer Center Support Grant (P30-CA076292)
- The Moffitt Foundation (N/A)
- The Miriam and Sheldon G. Adelson Medical Research Foundation (N/A)
- Immunology Innovation Fund (N/A)
This publication has 22 references indexed in Scilit:
- Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancersOncotarget, 2014
- Alterations of immune response of non-small cell lung cancer with AzacytidineOncotarget, 2013
- Molecular mechanisms of T cell co-stimulation and co-inhibitionNature Reviews Immunology, 2013
- The blockade of immune checkpoints in cancer immunotherapyNature Reviews Cancer, 2012
- Chemokine Expression in Melanoma Metastases Associated with CD8+ T-Cell RecruitmentCancer Research, 2009
- DNA methylation landscapes: provocative insights from epigenomicsNature Reviews Genetics, 2008
- Low Surface Expression of B7-1 (CD80) Is an Immunoescape Mechanism of Colon CarcinomaCancer Research, 2006
- DNA Methylation and Cancer-associated Genetic InstabilityAdvances in experimental medicine and biology, 2004
- Methylation and demethylation in the regulation of genes, cells, and responses in the immune systemClinical Immunology, 2003
- DNA hypermethylation is a mechanism for loss of expression of the HLA class I genes in human esophageal squamous cell carcinomasCarcinogenesis: Integrative Cancer Research, 2001