Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients

<div><p>T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related c...

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Main Author: Alhasan Alsalman (14802873) (author)
Other Authors: Mohammad A. Al-Mterin (18420798) (author), Khaled Murshed (8309781) (author), Ferial Alloush (18420801) (author), Samia T. Al-Shouli (12966140) (author), Salman M. Toor (8854751) (author), Eyad Elkord (5396390) (author)
Published: 2022
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_version_ 1864513518727856128
author Alhasan Alsalman (14802873)
author2 Mohammad A. Al-Mterin (18420798)
Khaled Murshed (8309781)
Ferial Alloush (18420801)
Samia T. Al-Shouli (12966140)
Salman M. Toor (8854751)
Eyad Elkord (5396390)
author2_role author
author
author
author
author
author
author_facet Alhasan Alsalman (14802873)
Mohammad A. Al-Mterin (18420798)
Khaled Murshed (8309781)
Ferial Alloush (18420801)
Samia T. Al-Shouli (12966140)
Salman M. Toor (8854751)
Eyad Elkord (5396390)
author_role author
dc.creator.none.fl_str_mv Alhasan Alsalman (14802873)
Mohammad A. Al-Mterin (18420798)
Khaled Murshed (8309781)
Ferial Alloush (18420801)
Samia T. Al-Shouli (12966140)
Salman M. Toor (8854751)
Eyad Elkord (5396390)
dc.date.none.fl_str_mv 2022-06-29T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/cancers14133194
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Circulating_and_Tumor-Infiltrating_Immune_Checkpoint-Expressing_CD8_Treg_T_Cell_Subsets_and_Their_Associations_with_Disease-Free_Survival_in_Colorectal_Cancer_Patients/25662630
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
Oncology and carcinogenesis
CD8+ T cells
TILs
PBMCs
Progression-Free Survival
immune checkpoints
Tregs
dc.title.none.fl_str_mv Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related cancers such as colorectal cancer (CRC). In this study, we phenotypically characterized CD3+CD4- (CD8+) T cells in colorectal tumor tissues (TT), normal colon tissues (NT) and in circulation of CRC patients. We investigated the expression levels of key immune checkpoints (ICs) and Treg-related markers in CD8+ T cells. Importantly, we investigated associations between different tumor-infiltrating CD8+ T cell subpopulations and disease-free survival (DFS) in CRC patients. We found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly increased in tumor-infiltrating CD8+ T cells compared with NT and peripheral blood. In the TME, we found that TIM-3 expression was significantly increased in patients with early stages and absent lymphovascular invasion (LVI) compared to patients with advanced stages and LVI. Importantly, we report that high levels of certain circulating CD8+ T cell subsets (TIM-3-expressing, FoxP3−Helios−TIM-3+ and FoxP3−Helios+TIM-3+ cells) in CRC patients were associated with better DFS. Moreover, in the TME, we report that elevated levels of CD25+ and TIM-3+ T cells, and FoxP3+Helios−TIM-3+ Tregs were associated with better DFS.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Cancers<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="https://dx.doi.org/10.3390/cancers14133194" target="_blank">https://dx.doi.org/10.3390/cancers14133194</a></p>
eu_rights_str_mv openAccess
id Manara2_e6260339a0f310492e8d1446249f6c52
identifier_str_mv 10.3390/cancers14133194
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25662630
publishDate 2022
repository.mail.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer PatientsAlhasan Alsalman (14802873)Mohammad A. Al-Mterin (18420798)Khaled Murshed (8309781)Ferial Alloush (18420801)Samia T. Al-Shouli (12966140)Salman M. Toor (8854751)Eyad Elkord (5396390)Biomedical and clinical sciencesOncology and carcinogenesisCD8+ T cellsTILsPBMCsProgression-Free Survivalimmune checkpointsTregs<div><p>T cells in the tumor microenvironment (TME) have diverse roles in anti-tumor immunity, including orchestration of immune responses and anti-tumor cytotoxic attack. However, different T cell subsets may have opposing roles in tumor progression, especially in inflammation-related cancers such as colorectal cancer (CRC). In this study, we phenotypically characterized CD3+CD4- (CD8+) T cells in colorectal tumor tissues (TT), normal colon tissues (NT) and in circulation of CRC patients. We investigated the expression levels of key immune checkpoints (ICs) and Treg-related markers in CD8+ T cells. Importantly, we investigated associations between different tumor-infiltrating CD8+ T cell subpopulations and disease-free survival (DFS) in CRC patients. We found that FoxP3 expression and ICs including PD-1, CTLA-4, TIM-3, and LAG-3 were significantly increased in tumor-infiltrating CD8+ T cells compared with NT and peripheral blood. In the TME, we found that TIM-3 expression was significantly increased in patients with early stages and absent lymphovascular invasion (LVI) compared to patients with advanced stages and LVI. Importantly, we report that high levels of certain circulating CD8+ T cell subsets (TIM-3-expressing, FoxP3−Helios−TIM-3+ and FoxP3−Helios+TIM-3+ cells) in CRC patients were associated with better DFS. Moreover, in the TME, we report that elevated levels of CD25+ and TIM-3+ T cells, and FoxP3+Helios−TIM-3+ Tregs were associated with better DFS.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Cancers<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="https://dx.doi.org/10.3390/cancers14133194" target="_blank">https://dx.doi.org/10.3390/cancers14133194</a></p>2022-06-29T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/cancers14133194https://figshare.com/articles/journal_contribution/Circulating_and_Tumor-Infiltrating_Immune_Checkpoint-Expressing_CD8_Treg_T_Cell_Subsets_and_Their_Associations_with_Disease-Free_Survival_in_Colorectal_Cancer_Patients/25662630CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256626302022-06-29T03:00:00Z
spellingShingle Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
Alhasan Alsalman (14802873)
Biomedical and clinical sciences
Oncology and carcinogenesis
CD8+ T cells
TILs
PBMCs
Progression-Free Survival
immune checkpoints
Tregs
status_str publishedVersion
title Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
title_full Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
title_fullStr Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
title_full_unstemmed Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
title_short Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
title_sort Circulating and Tumor-Infiltrating Immune Checkpoint-Expressing CD8+ Treg/T Cell Subsets and Their Associations with Disease-Free Survival in Colorectal Cancer Patients
topic Biomedical and clinical sciences
Oncology and carcinogenesis
CD8+ T cells
TILs
PBMCs
Progression-Free Survival
immune checkpoints
Tregs