{"id":"doi:10.1371/journal.pone.0030676","kind":"article","title":"TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression","authors":["Gao X","Zhu Y","Li G","Huang H","Zhang G","Wang F","Sun J","Yang Q","Zhang X","Lu B"],"author_count":10,"year":2012,"published":"2012-02-17","venue":"PloS one","cited_by":338,"doi":"10.1371/journal.pone.0030676","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1371/journal.pone.0030676","archive_url":"https://space-kitty.com/papers/doi:10.1371/journal.pone.0030676","updated":null,"pmid":"22363469","pmcid":"PMC3281852","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC3281852/pdf","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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression\" by Gao X, Zhu Y, Li G et al., https://doi.org/10.1371/journal.pone.0030676, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}