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Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer

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Version 2 2024-07-14, 11:41
Version 1 2022-11-22, 21:11
journal contribution
posted on 2022-11-22, 21:11 authored by Reem Saleh, Rowaida Z. Taha, Salman M. Toor, Varun Sasidharan Nair, Khaled Murshed, Mahwish Khawar, Mahmood Al-Dhaheri, Mahir Abdulla Petkar, Mohamed Abu Nada, Eyad Elkord

Despite recent advances in colorectal cancer (CRC) treatment, a large proportion of patients show limited responses to therapies, especially in advanced stages. There is an urgent need to identify prognostic biomarkers and/or therapeutic targets in advanced stages, aiming to improve the efficacy of current treatments. We aimed to determine prognostic biomarkers in tumor tissue and circulation of CRC patients, with a special focus on T cell exhaustion markers. We found that mRNA levels of PD-1, TIM-3, CTLA-4, TIGIT, CD160, CD244, KLRG1, TOX2, TOX3, Ki-67, and PRDM1 were elevated in CRC tumor tissues. We also investigated differences in gene expression between early and advanced disease stages. We found that TOX and potentially TIM-3, CTLA-4, VISTA, TIGIT, KLRG1, TOX2, SIRT1, Ki-67, and Helios mRNA levels in tumor tissue were elevated in advanced disease stages, suggesting their potential roles in CRC progression. In contrast, PD-1 and CD160 levels in tumor tissue were downregulated in advanced stages. In the circulation of CRC patients, mRNA levels of PD-1, VISTA and LAG-3 were higher than those of healthy individuals. Moreover, in circulation, PD-1, CTLA-4 and TIGIT mRNA levels were reduced in advanced stages. Interestingly, levels of PD-1 in both tumor tissue and circulation were reduced in advanced stages, suggesting that targeting PD-1 in patients with advanced stages could be less effective. Altogether, these findings suggest some potential T cell exhaustion markers that could be utilized as prognostic biomarkers and/or therapeutic targets for CRC. However, further investigations and validations in larger cohorts are required to confirm these findings.

Other Information

Published in: Cancer Immunology, Immunotherapy
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: http://dx.doi.org/10.1007/s00262-020-02593-w

History

Language

  • English

Publisher

Springer Science and Business Media LLC

Publication Year

  • 2020

Institution affiliated with

  • Hamad Bin Khalifa University

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    Qatar Biomedical Research Institute - HBKU

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