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TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression

Gao, X and Zhu, Y and Li, G and Huang, H and Zhang, G and Wang, F and Sun, J and Yang, Q and Zhang, X and Lu, B (2012) TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS ONE, 7 (2).

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Abstract

Background: 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. Methodology: 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. Conclusions: 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-3 +CD8 + TILs compared to TIM-3 -CD8 + 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-3 +CD4 + 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. © 2012 Gao et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Gao, X
Zhu, Y
Li, G
Huang, H
Zhang, G
Wang, F
Sun, J
Yang, Q
Zhang, X
Lu, Bbinfeng@pitt.eduBINFENG
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBachmann, Michael P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 17 February 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 2
DOI or Unique Handle: 10.1371/journal.pone.0030676
Schools and Programs: School of Medicine > Immunology
Refereed: Yes
MeSH Headings: Animals; CD8-Positive T-Lymphocytes--immunology; Carcinoma, Non-Small-Cell Lung--immunology; Carcinoma, Non-Small-Cell Lung--pathology; Disease Models, Animal; Disease Progression; Female; Humans; Interferon-gamma--biosynthesis; Lung Neoplasms--immunology; Lung Neoplasms--pathology; Lymphocyte Activation--immunology; Lymphocytes, Tumor-Infiltrating--immunology; Membrane Proteins--metabolism; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; T-Lymphocytes, Regulatory--immunology; Up-Regulation--immunology
Other ID: NLM PMC3281852
PubMed Central ID: PMC3281852
PubMed ID: 22363469
Date Deposited: 13 Sep 2012 17:57
Last Modified: 04 Feb 2019 15:59
URI: http://d-scholarship.pitt.edu/id/eprint/14140

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