Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy

Targeting DNA Methylation and EZH2 Activity to Overcome Melanoma Resistance to Immunotherapy.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Trends in Immunology
Volume: 40
Number: 4
Page Range: pp. 328-344
Date: 2019
Divisions: Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.1016/
ISSN: 14714906
Date Deposited: 04 Jan 2021 23:42

Genome-wide DNA methylation is a relatively stable epigenetic characteristic of cells, which can be dysregulated in cancer cells by oncogenic signals.

Hyper- or hypomethylation of DNA in melanoma cells underlies the categorization of melanoma patients into four groups according to PD-L1 expression and T cell infiltration.

Resistance of melanoma to immunotherapy by immune checkpoint inhibitors is associated with global hypermethylation and low PD-L1 expression whereas global hypomethylation is associated with constitutive PD-L1 expression and inhibitory cytokine production.

Hypermethylation of DNA in melanoma is associated with overexpression of DNA methyltransferases (DNMTs) and histone methyltransferase-EZH2 in the PRC2 repressive complex.

The T cell exhaustion state is associated with hypomethylation of PD1, LAG3, and TIM3 promoters. EZH2 can be activated by the YY1 transcription factor in human melanoma cells, downregulating the IL2 promoter by de novo methylation.

Emran, Abdullah Al
Chatterjee, Aniruddha
Rodger, Euan J.
Tiffen, Jessamy C.
Gallagher, Stuart J.
Eccles, Michael R.
Hersey, Peter
Last Modified: 04 Jan 2021 23:42

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