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PLoS One. 2012;7(2):e30676. doi: 10.1371/journal.pone.0030676. Epub 2012 Feb 17.

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

Author information

1
Department of Immunology, Institute of Medical Biotechnology, Soochow University, Suzhou, People's Republic of China.

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.

PMID:
22363469
PMCID:
PMC3281852
DOI:
10.1371/journal.pone.0030676
[Indexed for MEDLINE]
Free PMC Article

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