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TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression (TIM-3 + Tregs Associate with Lung Cancer Severity)

T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 + CD4 + T cells in the tumor microenvironment is unc... Full description

Journal Title: PLoS ONE 2012, Vol.7(2), p.e30676
Main Author: Gao, Xin
Other Authors: Zhu, Yibei , Li, Gang , Huang, Haitao , Zhang, Guangbo , Wang, Fengming , Sun, Jing , Yang, Qianting , Zhang, Xueguang , Lu, Binfeng
Format: Electronic Article Electronic Article
Language: English
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ID: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0030676
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recordid: plos10.1371/journal.pone.0030676
title: TIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression (TIM-3 + Tregs Associate with Lung Cancer Severity)
format: Article
creator:
  • Gao, Xin
  • Zhu, Yibei
  • Li, Gang
  • Huang, Haitao
  • Zhang, Guangbo
  • Wang, Fengming
  • Sun, Jing
  • Yang, Qianting
  • Zhang, Xueguang
  • Lu, Binfeng
subjects:
  • Research Article
  • Biology
  • Medicine
  • Immunology
  • Oncology
ispartof: PLoS ONE, 2012, Vol.7(2), p.e30676
description: T cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 + CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. ; A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. ; TIM-3 is highly upregulated on both CD4 and CD8 TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ cells were reduced in TIM-3CD8 TILs compared to TIM-3CD8 TILs. However, the level of TIM-3 expression on CD8 TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3CD4 TILs expressed FOXP3 and about 60% of FOXP3 TILs were TIM-3. Importantly, TIM-3 expression on CD4 T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells.
language: eng
source:
identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0030676
fulltext: fulltext
issn:
  • 1932-6203
  • 19326203
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titleTIM-3 Expression Characterizes Regulatory T Cells in Tumor Tissues and Is Associated with Lung Cancer Progression (TIM-3 + Tregs Associate with Lung Cancer Severity)
creatorGao, Xin ; Zhu, Yibei ; Li, Gang ; Huang, Haitao ; Zhang, Guangbo ; Wang, Fengming ; Sun, Jing ; Yang, Qianting ; Zhang, Xueguang ; Lu, Binfeng
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descriptionT cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 + CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. ; A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. ; TIM-3 is highly upregulated on both CD4 and CD8 TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ cells were reduced in TIM-3CD8 TILs compared to TIM-3CD8 TILs. However, the level of TIM-3 expression on CD8 TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3CD4 TILs expressed FOXP3 and about 60% of FOXP3 TILs were TIM-3. Importantly, TIM-3 expression on CD4 T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells.
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abstractT cell immunoglobulin-3 (TIM-3) has been established as a negative regulatory molecule and plays a critical role in immune tolerance. TIM-3 is upregulated in exhausted CD8 + T cells in both chronic infection and tumor. However, the nature of TIM-3 + CD4 + T cells in the tumor microenvironment is unclear. This study is to characterize TIM-3 expressing lymphocytes within human lung cancer tissues and establish clinical significance of TIM-3 expression in lung cancer progression. ; A total of 51 human lung cancer tissue specimens were obtained from pathologically confirmed and newly diagnosed non-small cell lung cancer (NSCLC) patients. Leukocytes from tumor tissues, distal normal lung tissues, and peripheral blood mononuclear cells (PBMC) were analyzed for TIM-3 surface expression by flow cytometry. TIM-3 expression on tumor-infiltrating lymphocytes (TILs) was correlated with clinicopathological parameters. ; TIM-3 is highly upregulated on both CD4 and CD8 TILs from human lung cancer tissues but negligibly expressed on T cells from patients' peripheral blood. Frequencies of IFN-γ cells were reduced in TIM-3CD8 TILs compared to TIM-3CD8 TILs. However, the level of TIM-3 expression on CD8 TILs failed to associate with any clinical pathological parameter. Interestingly, we found that approximately 70% of TIM-3CD4 TILs expressed FOXP3 and about 60% of FOXP3 TILs were TIM-3. Importantly, TIM-3 expression on CD4 T cells correlated with poor clinicopathological parameters of NSCLC such as nodal metastasis and advanced cancer stages. Our study reveals a new role of TIM-3 as an important immune regulator in the tumor microenvironment via its predominant expression in regulatory T cells.
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doi10.1371/journal.pone.0030676
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date2012-02-17