Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer
<p>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 eff...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , , , , |
| منشور في: |
2020
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| الموضوعات: | |
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| _version_ | 1864513510865633280 |
|---|---|
| author | Reem Saleh (3513056) |
| author2 | Rowaida Z. Taha (8854754) Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Khaled Murshed (8309781) Mahwish Khawar (9621038) Mahmood Al-Dhaheri (9621035) Mahir Abdulla Petkar (14150211) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author2_role | author author author author author author author author author |
| author_facet | Reem Saleh (3513056) Rowaida Z. Taha (8854754) Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Khaled Murshed (8309781) Mahwish Khawar (9621038) Mahmood Al-Dhaheri (9621035) Mahir Abdulla Petkar (14150211) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| author_role | author |
| dc.creator.none.fl_str_mv | Reem Saleh (3513056) Rowaida Z. Taha (8854754) Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Khaled Murshed (8309781) Mahwish Khawar (9621038) Mahmood Al-Dhaheri (9621035) Mahir Abdulla Petkar (14150211) Mohamed Abu Nada (8309784) Eyad Elkord (5396390) |
| dc.date.none.fl_str_mv | 2020-05-11T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s00262-020-02593-w |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Expression_of_immune_checkpoints_and_T_cell_exhaustion_markers_in_early_and_advanced_stages_of_colorectal_cancer/21596952 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Colorectal cancer Immune checkpoints T cell exhaustion Prognostic biomarker Therapeutic target |
| dc.title.none.fl_str_mv | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>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.</p><h2>Other Information</h2> <p> Published in: Cancer Immunology, Immunotherapy<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s00262-020-02593-w" target="_blank">http://dx.doi.org/10.1007/s00262-020-02593-w</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_5c37e9289cf52cde0902a2bfbde775a8 |
| identifier_str_mv | 10.1007/s00262-020-02593-w |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/21596952 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancerReem Saleh (3513056)Rowaida Z. Taha (8854754)Salman M. Toor (8854751)Varun Sasidharan Nair (5396393)Khaled Murshed (8309781)Mahwish Khawar (9621038)Mahmood Al-Dhaheri (9621035)Mahir Abdulla Petkar (14150211)Mohamed Abu Nada (8309784)Eyad Elkord (5396390)Biomedical and clinical sciencesImmunologyOncology and carcinogenesisColorectal cancerImmune checkpointsT cell exhaustionPrognostic biomarkerTherapeutic target<p>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.</p><h2>Other Information</h2> <p> Published in: Cancer Immunology, Immunotherapy<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s00262-020-02593-w" target="_blank">http://dx.doi.org/10.1007/s00262-020-02593-w</a></p>2020-05-11T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s00262-020-02593-whttps://figshare.com/articles/journal_contribution/Expression_of_immune_checkpoints_and_T_cell_exhaustion_markers_in_early_and_advanced_stages_of_colorectal_cancer/21596952CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215969522020-05-11T06:00:00Z |
| spellingShingle | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer Reem Saleh (3513056) Biomedical and clinical sciences Immunology Oncology and carcinogenesis Colorectal cancer Immune checkpoints T cell exhaustion Prognostic biomarker Therapeutic target |
| status_str | publishedVersion |
| title | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| title_full | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| title_fullStr | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| title_full_unstemmed | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| title_short | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| title_sort | Expression of immune checkpoints and T cell exhaustion markers in early and advanced stages of colorectal cancer |
| topic | Biomedical and clinical sciences Immunology Oncology and carcinogenesis Colorectal cancer Immune checkpoints T cell exhaustion Prognostic biomarker Therapeutic target |