Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer
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ORIGINAL ARTICLE
Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer Reem Saleh1 · Rowaida Z. Taha1 · Salman M. Toor1 · Varun Sasidharan Nair1 · Khaled Murshed2 · Mahwish Khawar3 · Mahmood Al‑Dhaheri3 · Mahir Abdulla Petkar2 · Mohamed Abu Nada3 · Eyad Elkord1 Received: 16 February 2020 / Accepted: 27 April 2020 © The Author(s) 2020
Abstract 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. Keywords Colorectal cancer · Immune checkpoints · T cell exhaustion · Prognostic biomarker · Therapeutic target Abbreviations Blimp1 B lymphocyte-induced maturation protein-1 CRC Colorectal cancer CTLA-4 Cytotoxic T-lymphocyte-associated protein 4 KLRG1 Killer cell lectin-like receptor subfamily G member 1 LAG-3 Lymphocyte-activation gene 3 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02593-w) contains supplementary material, which is available to authorized users. * Eyad Elkord [email protected]; [email protected] 1
Cancer Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation (QF), P.O. Box: 34110, Doha, Qatar
2
Department of Pathology, Hamad Medical Corporation, Doha, Qatar
3
Department of Surgery, Hamad Medical Corporation, Doha, Qatar
PBMC Peripheral blood mononuclear cell PD-1 Programmed cell death-1 PRDM1
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