Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients

<p dir="ltr">Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation wi...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Salman M. Toor (8854751) (author)
مؤلفون آخرون: Azharuddin Sajid Syed Khaja (19720114) (author), Haytham El Salhat (5396387) (author), Omar Bekdache (19730857) (author), Jihad Kanbar (19720192) (author), Mohammed Jaloudi (19730860) (author), Eyad Elkord (5396390) (author)
منشور في: 2016
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author Salman M. Toor (8854751)
author2 Azharuddin Sajid Syed Khaja (19720114)
Haytham El Salhat (5396387)
Omar Bekdache (19730857)
Jihad Kanbar (19720192)
Mohammed Jaloudi (19730860)
Eyad Elkord (5396390)
author2_role author
author
author
author
author
author
author_facet Salman M. Toor (8854751)
Azharuddin Sajid Syed Khaja (19720114)
Haytham El Salhat (5396387)
Omar Bekdache (19730857)
Jihad Kanbar (19720192)
Mohammed Jaloudi (19730860)
Eyad Elkord (5396390)
author_role author
dc.creator.none.fl_str_mv Salman M. Toor (8854751)
Azharuddin Sajid Syed Khaja (19720114)
Haytham El Salhat (5396387)
Omar Bekdache (19730857)
Jihad Kanbar (19720192)
Mohammed Jaloudi (19730860)
Eyad Elkord (5396390)
dc.date.none.fl_str_mv 2016-12-08T03:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fimmu.2016.00560
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Increased_Levels_of_Circulating_and_Tumor-Infiltrating_Granulocytic_Myeloid_Cells_in_Colorectal_Cancer_Patients/27094651
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
myeloid cells
neutrophils
colorectal cancer
circulation
tumor microenvironment
dc.title.none.fl_str_mv Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment (TME) of colorectal cancer (CRC) patients, compared to blood from healthy donors (HDs) and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of cells expressing myeloid markers and lacking the expression of major histocompatibility complex class II molecule HLA-DR in blood and tumor of CRC patients. Further analysis revealed that these cells were granulocytic and expressed Arginase 1 indicative of their suppressive phenotype. These expanded cells could be neutrophils or granulocytic MDSCs, and we refer to them as granulocytic myeloid cells (GMCs) due to the phenotypical and functional overlap between these cell subsets. Interestingly, the expansion of peripheral GMCs correlated with higher stage and histological grade of cancer, thereby suggesting their role in cancer progression. Furthermore, an increase in CD33<sup>+</sup>CD11b<sup>+</sup>HLA-DR<sup>−</sup>CD14<sup>−</sup>CD15<sup>−</sup> immature myeloid cells was also observed in CRC tumor tissue. Our work shows that GMCs are expanded in circulation and TME of CRC patients, which provides further insights for developing immunotherapeutic approaches targeting these cell subsets to enhance antitumor immune and clinical responses.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" rel="noreferrer noopener" target="_blank">https://creativecommons.org/licenses/by/4.0/</a>  <br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2016.00560" target="_blank">https://dx.doi.org/10.3389/fimmu.2016.00560</a></p>
eu_rights_str_mv openAccess
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network_acronym_str Manara2
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oai_identifier_str oai:figshare.com:article/27094651
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spelling Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer PatientsSalman M. Toor (8854751)Azharuddin Sajid Syed Khaja (19720114)Haytham El Salhat (5396387)Omar Bekdache (19730857)Jihad Kanbar (19720192)Mohammed Jaloudi (19730860)Eyad Elkord (5396390)Biomedical and clinical sciencesImmunologyOncology and carcinogenesismyeloid cellsneutrophilscolorectal cancercirculationtumor microenvironment<p dir="ltr">Increased levels of myeloid cells, especially myeloid-derived suppressor cells (MDSCs), have been reported to correlate with bad prognosis and reduced survival in cancer patients. However, limited data are available on their conclusive phenotypes and their correlation with clinical settings. The aim of this study was to investigate levels and phenotype of myeloid cells in peripheral blood and tumor microenvironment (TME) of colorectal cancer (CRC) patients, compared to blood from healthy donors (HDs) and paired, adjacent non-tumor colon tissue. Flow cytometric analysis was performed to examine the expression of different myeloid markers in fresh peripheral blood samples from CRC patients and HDs, and tissue-infiltrating immune cells from CRC patients. We found significantly higher levels of cells expressing myeloid markers and lacking the expression of major histocompatibility complex class II molecule HLA-DR in blood and tumor of CRC patients. Further analysis revealed that these cells were granulocytic and expressed Arginase 1 indicative of their suppressive phenotype. These expanded cells could be neutrophils or granulocytic MDSCs, and we refer to them as granulocytic myeloid cells (GMCs) due to the phenotypical and functional overlap between these cell subsets. Interestingly, the expansion of peripheral GMCs correlated with higher stage and histological grade of cancer, thereby suggesting their role in cancer progression. Furthermore, an increase in CD33<sup>+</sup>CD11b<sup>+</sup>HLA-DR<sup>−</sup>CD14<sup>−</sup>CD15<sup>−</sup> immature myeloid cells was also observed in CRC tumor tissue. Our work shows that GMCs are expanded in circulation and TME of CRC patients, which provides further insights for developing immunotherapeutic approaches targeting these cell subsets to enhance antitumor immune and clinical responses.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/deed.en" rel="noreferrer noopener" target="_blank">https://creativecommons.org/licenses/by/4.0/</a>  <br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2016.00560" target="_blank">https://dx.doi.org/10.3389/fimmu.2016.00560</a></p>2016-12-08T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2016.00560https://figshare.com/articles/journal_contribution/Increased_Levels_of_Circulating_and_Tumor-Infiltrating_Granulocytic_Myeloid_Cells_in_Colorectal_Cancer_Patients/27094651CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/270946512016-12-08T03:00:00Z
spellingShingle Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
Salman M. Toor (8854751)
Biomedical and clinical sciences
Immunology
Oncology and carcinogenesis
myeloid cells
neutrophils
colorectal cancer
circulation
tumor microenvironment
status_str publishedVersion
title Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
title_full Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
title_fullStr Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
title_full_unstemmed Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
title_short Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
title_sort Increased Levels of Circulating and Tumor-Infiltrating Granulocytic Myeloid Cells in Colorectal Cancer Patients
topic Biomedical and clinical sciences
Immunology
Oncology and carcinogenesis
myeloid cells
neutrophils
colorectal cancer
circulation
tumor microenvironment