Epigenetic regulation of immune checkpoints and T cell exhaustion markers in tumor-infiltrating T cells of colorectal cancer patients

Nair, VS ORCID: https://orcid.org/0000-0001-5047-2338, Saleh, R ORCID: https://orcid.org/0000-0002-8292-1895, Toor, SM ORCID: https://orcid.org/0000-0002-4683-3329, Taha, RZ ORCID: https://orcid.org/0000-0001-6119-8389, Ahmed, AA, Kurer, MA, Murshed, K ORCID: https://orcid.org/0000-0001-8045-363X, Nada, MA and Elkord, E ORCID: https://orcid.org/0000-0002-3868-0318 2020, 'Epigenetic regulation of immune checkpoints and T cell exhaustion markers in tumor-infiltrating T cells of colorectal cancer patients' , Epigenomics, 12 (21) , pp. 1871-1882.

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Abstract

Aim: To elucidate the epigenetic alterations behind the upregulation of immune checkpoints and T cell exhaustion markers in colorectal cancer (CRC) patients. Materials & methods: mRNA expressions of different immune checkpoint/exhaustion markers were analyzed by quantitative real-time reverse transcriptase PCR and epigenetic investigations were performed using bisulfite sequencing and chromatin immunoprecipitation quantitative PCR. Results: mRNA expressions of PD-1, TIM-3, CTLA-4, PD-L1 and TOX2 were significantly upregulated in CD4+ and CD8+ tumor-infiltrating lymphocytes and bulk CRC tumor tissues. Histone 3 lysine 9 trimethylation was downregulated and histone 3 lysine 4 trimethylation was upregulated in PD-L1 and TOX2 promoters in tumor tissues, suggesting that PD-L1 and TOX2 upregulation in CRC tumors could be mediated by activating histone 3 lysine 4 trimethylation. Conclusion: Epigenetic modifications in promoters of immune checkpoint and T cell exhaustion genes could induce their upregulation, and potentially implicate the use of epigenetic modifiers to enhance antitumor immunity in CRC patients.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Epigenomics
Publisher: Future Medicine Ltd
ISSN: 1750-1911
Related URLs:
Funders: Qatar Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 18 Dec 2020 09:31
Last Modified: 18 Dec 2020 09:31
URI: http://usir.salford.ac.uk/id/eprint/59130

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