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

Nair, VS; Saleh, R; Toor, SM; Taha, RZ; Ahmed, AA; Kurer, MA; Murshed, K; Nada, MA; Elkord, E

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.

Citation

Nair, V., Saleh, R., Toor, S., Taha, R., Ahmed, A., Kurer, M., …Elkord, E. (2020). Epigenetic regulation of immune checkpoints and T cell exhaustion markers in tumor-infiltrating T cells of colorectal cancer patients. Epigenomics, 12(21), 1871-1882. https://doi.org/10.2217/epi-2020-0267

• Journal Article Type: Article
• Acceptance Date: Sep 17, 2020
• Online Publication Date: Nov 10, 2020
• Publication Date: Nov 10, 2020
• Deposit Date: Dec 18, 2020
• Journal: Epigenomics
• Print ISSN: 1750-1911
• Electronic ISSN: 1750-192X
• Publisher: Future Medicine
• Volume: 12
• Issue: 21
• Pages: 1871-1882
• DOI: https://doi.org/10.2217/epi-2020-0267
• Publisher URL: https://doi.org/10.2217/epi-2020-0267
• Related Public URLs: http://www.futuremedicine.com/loi/epi
• Additional Information: Funders : Qatar Foundation; Projects : VR04