The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer

ObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with...

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Main Authors: Zi-Xin Wu, Fei Wang, Liang Li, Yuan Yao, Jie Long, Qing-Qing Luo, Zhi-Bin Zhao, Wang-Lin Li, Jie Cao, Zhe-Xiong Lian
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.685577/full
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author Zi-Xin Wu
Zi-Xin Wu
Fei Wang
Fei Wang
Liang Li
Yuan Yao
Jie Long
Qing-Qing Luo
Qing-Qing Luo
Zhi-Bin Zhao
Wang-Lin Li
Wang-Lin Li
Jie Cao
Zhe-Xiong Lian
author_facet Zi-Xin Wu
Zi-Xin Wu
Fei Wang
Fei Wang
Liang Li
Yuan Yao
Jie Long
Qing-Qing Luo
Qing-Qing Luo
Zhi-Bin Zhao
Wang-Lin Li
Wang-Lin Li
Jie Cao
Zhe-Xiong Lian
author_sort Zi-Xin Wu
collection DOAJ
description ObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.MethodsFlow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.ResultsWe found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.ConclusionThe mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.
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spelling doaj.art-947b6cce7a1f4fa69a363d5a112cfc5f2022-12-21T22:05:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-09-011110.3389/fonc.2021.685577685577The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal CancerZi-Xin Wu0Zi-Xin Wu1Fei Wang2Fei Wang3Liang Li4Yuan Yao5Jie Long6Qing-Qing Luo7Qing-Qing Luo8Zhi-Bin Zhao9Wang-Lin Li10Wang-Lin Li11Jie Cao12Zhe-Xiong Lian13Department of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaDepartment of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Colorectal Surgery, The Second Affiliated Hospital of South China University of Technology, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaObjectiveThe mesentery is a potential site of residual tumor in patients with colorectal cancer (CRC). However, the mesenteric immune microenvironment remains unclear. In this study, we investigated the immune landscape of the mesentery, particularly the role of lymphocytes and its association with the clinicopathological characteristics of CRC.MethodsFlow cytometry was used to detect lymphocytes in the paired mesenteric tissue specimens adjacent to the colorectal tumors and normal mesenteric tissue specimens 10 cm away from the colorectal tumor edge and preoperative peripheral blood samples obtained from patients with CRC who underwent surgery. T-distributed stochastic neighbor embedding was utilized to analyze multiparameter flow cytometry data. Multiplex immunohistochemistry was performed to evaluate T cells subsets in the paired mesentery adjacent to the colorectal tumors and normal mesentery. The Fisher’s exact test and non-parametric Wilcoxon’s matched-pairs tests were used for statistical analysis. The non-parametric Mann-Whitney U test was used to determine associations between percentage data and clinical parameters of patients with CRC.ResultsWe found that immune cells in the normal mesentery were mainly of lymphoid lineage. Compared with peripheral blood, the normal mesentery showed decreased NK cells and the CD4/CD8 ratio and increased CD3+ CD56+, memory CD4+ T, memory CD8+ T, CD4+ tissue-resident memory T (TRM), and CD8+ TRM cells. Compared with the normal mesentery, the mesentery adjacent to the colorectal tumor showed increased B and regulatory T cells and decreased NK, CD3+ CD56+, CD4+ TRM, and CD8+ TRM cells. Moreover, memory CD8+ T cells and plasmablasts are negatively correlated with the depth of invasion of CRC. Increased memory CD4+ T cells are associated with distant metastasis of CRC and high preoperative serum carcinoembryonic antigen levels.ConclusionThe mesentery shows a specific immune microenvironment, which differs from that observed in peripheral blood. CRC can alter the mesenteric immune response to promote tumor progression.https://www.frontiersin.org/articles/10.3389/fonc.2021.685577/fullcolorectal cancerclinical significanceimmune microenvironmentlymphocytemesentery
spellingShingle Zi-Xin Wu
Zi-Xin Wu
Fei Wang
Fei Wang
Liang Li
Yuan Yao
Jie Long
Qing-Qing Luo
Qing-Qing Luo
Zhi-Bin Zhao
Wang-Lin Li
Wang-Lin Li
Jie Cao
Zhe-Xiong Lian
The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
Frontiers in Oncology
colorectal cancer
clinical significance
immune microenvironment
lymphocyte
mesentery
title The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
title_full The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
title_fullStr The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
title_full_unstemmed The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
title_short The Clinical Significance of Mesenteric Lymphocytes in Human Colorectal Cancer
title_sort clinical significance of mesenteric lymphocytes in human colorectal cancer
topic colorectal cancer
clinical significance
immune microenvironment
lymphocyte
mesentery
url https://www.frontiersin.org/articles/10.3389/fonc.2021.685577/full
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