Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1 Expression in Melanoma

Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1 Expression in Melanoma.

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.1016/j.isci.2018.05.021
Journal or Publication Title: iScience
Volume: 4
Page Range: pp. 312-325
Date: 2018
Divisions: Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.1016/j.isci.2018.05.021
ISSN: 25890042
Date Deposited: 03 Jan 2021 22:57
Abstract:

Constitutive expression of the immune checkpoint, PD-L1, inhibits anti-tumor immune responses in cancer, although the factors involved in PD-L1 regulation are poorly understood. Here we show that loss of global DNA methylation, particularly in intergenic regions and repeat elements, is associated with constitutive (PD-L1CON), versus inducible (PD-L1IND), PD-L1 expression in melanoma cell lines. We further show this is accompanied by transcriptomic up-regulation. De novo epigenetic regulators (e.g., DNMT3A) are strongly correlated with PD-L1 expression and methylome status. Accordingly, decitabine-mediated inhibition of global methylation in melanoma cells leads to increased PD-L1 expression. Moreover, viral mimicry and immune response genes are highly expressed in lymphocyte-negative plus PD-L1-positive melanomas, versus PD-L1-negative melanomas in The Cancer Genome Atlas (TCGA). In summary, using integrated genomic analysis we identified that global DNA methylation influences PD-L1 expression in melanoma, and hence melanoma's ability to evade anti-tumor immune responses. These results have implications for combining epigenetic therapy with immunotherapy.

Keywords: Cancer; Genetics; Genomics; Transcriptomics.

Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Creators:
Creators
Email
Chatterjee, Aniruddha
UNSPECIFIED
Rodger, Euan J.
UNSPECIFIED
Ahn, Antonio
UNSPECIFIED
Stockwell, Peter A.
UNSPECIFIED
Parry, Matthew
UNSPECIFIED
Motwani, Jyoti
UNSPECIFIED
Gallagher, Stuart J.
UNSPECIFIED
Shklovskaya, Elena
UNSPECIFIED
Tiffen, Jessamy
UNSPECIFIED
Eccles, Michael R.
UNSPECIFIED
Hersey, Peter
UNSPECIFIED
Last Modified: 03 Jan 2021 22:57
URI: https://eprints.centenary.org.au/id/eprint/502

Actions (login required)

View Item View Item