• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    DNA methylation of immune checkpoints in the peripheral blood of breast and colorectal cancer patients.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Elashi, AA
    Sasidharan, N
    Taha, RZ
    Shaath, H
    Elkord, Eyad
    Affiliation
    Cancer Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    Aberrant expression of immune checkpoints (ICs) in cancer creates an immunosuppressive microenvironment, which supports immune evasion of tumor cells. We have recently reported that epigenetic modifications are critical for ICs expression in the tumor microenvironment (TME) of primary breast cancer (PBC) and colorectal cancer (CRC). Herein, we investigated transcriptomic expression of ICs (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT) and PD-L1 in peripheral blood of PBC and CRC patients, compared to healthy donors (HD). We found that expressions of TIM-3, TIGIT, PD-L1 were significantly upregulated, while LAG-3 expression was downregulated in peripheral blood of PBC and CRC patients. Demethylation enzymes TET2 and TET3 were also upregulated. In addition, promoter DNA methylation status of PD-1 was significantly hypermethylated, while PD-L1 was hypomethylated in PBC and CRC patients. Furthermore, TIGIT was significantly hypomethylated only in CRC patients. Remarkably, promoter methylation status of LAG-3, TIGIT and PD-L1 was in concordance with transcriptomic expression in CRC: the more the hypomethylation, the higher the expression. In comparison, we found that CTLA-4, TIM-3, TIGIT and PD-L1 in PBC, and CTLA-4 in CRC patients were significantly upregulated in peripheral blood, compared with tumor tissues of the same patients. However, demethylation status of all ICs was higher in TT, except for TIGIT in PBC, and CTLA-4 in CRC patients. These data indicate that the underlying mechanisms behind peripheral upregulation of PD-L1 and TIGIT in cancer patients could be due to aberrant promoter methylation profile. Moreover, demethylation inhibitors together with anti-PD-L1/anti-TIGIT could be a more efficient therapeutic strategy in cancer patients.
    Citation
    Elashi AA, Sasidharan Nair V, Taha RZ, Shaath H, Elkord E. DNA methylation of immune checkpoints in the peripheral blood of breast and colorectal cancer patients. Oncoimmunology. 2019;8(2):e1542918.
    Journal
    Oncoimmunology
    URI
    http://hdl.handle.net/10541/621609
    DOI
    10.1080/2162402X.2018.1542918
    PubMed ID
    30713804
    Additional Links
    https://dx.doi.org/10.1080/2162402X.2018.1542918
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1080/2162402X.2018.1542918
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • DNA methylation and repressive histones in the promoters of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, PD-L1, and galectin-9 genes in human colorectal cancer.
    • Authors: Sasidharan Nair V, Toor SM, Taha RZ, Shaath H, Elkord E
    • Issue date: 2018 Aug 6
    • DNA methylation and repressive H3K9 and H3K27 trimethylation in the promoter regions of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, and PD-L1 genes in human primary breast cancer.
    • Authors: Sasidharan Nair V, El Salhat H, Taha RZ, John A, Ali BR, Elkord E
    • Issue date: 2018
    • Co-expression of PD-1 with TIGIT or PD-1 with TIM-3 on tumor-infiltrating CD8(+) T cells showed synergistic effects on improved disease-free survival in treatment-naïve CRC patients.
    • Authors: Meyiah A, Mahmoodi Chalbatani G, Al-Mterin MA, Malekraeisi MA, Murshed K, Elkord E
    • Issue date: 2023 Jun
    • Immune Checkpoints in Circulating and Tumor-Infiltrating CD4(+) T Cell Subsets in Colorectal Cancer Patients.
    • Authors: Toor SM, Murshed K, Al-Dhaheri M, Khawar M, Abu Nada M, Elkord E
    • Issue date: 2019
    • Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression.
    • Authors: Saleh R, Toor SM, Sasidharan Nair V, Elkord E
    • Issue date: 2020
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.