title: The Clinical Significance of Abnormal Tim-3 Expression on NK Cells from Patients with Gastric Cancer.
abstract: OBJECTIVE
  To investigate the clinical significance of Tim-3 (T-cell immunoglobulin- and mucin-domain-containing molecule 3) expression in natural killer (NK) cells from patients with gastric cancer.
  
  
  METHODS
  Sixty-two patients with gastric cancer and 32 healthy controls were recruited for this study. Tim-3 expression in peripheral blood samples was analyzed using flow cytometry. The expression pattern of Tim-3 on NK cells was also confirmed using a gastric cancer-bearing mouse model. To further investigate the mechanisms that regulate Tim-3 expression, T-bet(-/-), Eomes(-/-), and Eomes/T-bet double knockout mice were utilized. Additionally, we statistically analyzed the clinical significance of Tim-3 expression on NK cells.
  
  
  RESULTS
  We found that the levels of Tim-3 in NK cells obtained from patients with gastric cancer were significantly higher than the levels in healthy controls. Clinical analyses showed that Tim-3 levels on NK cells were associated with advanced tumor stage. In a tumor-bearing mouse model, Tim-3 levels in NK cells increased with tumor growth, indicating that tumor progression could induce Tim-3 expression in NK cells. Finally, we report that T-bet is a key factor involved in regulating Tim-3 expression.
  
  
  CONCLUSIONS
  Our data indicate that Tim-3 expression on NK cells is regulated by T-bet, and that Tim-3 levels correlate with advanced stages of gastric cancer.
authors.affiliation: Department of Medical Oncology and.
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Wang
authors.forename: Jinlian
authors.initials: J
authors.lastname: Zhu
authors.forename: Haidi
authors.initials: H
authors.lastname: Gu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yibei
authors.initials: Y
authors.lastname: Zhu
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D011991:Receptors, Virus / Q000276:immunology*; D013274:Stomach Neoplasms / Q000276:immunology*; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: C448908:HAVCR2 protein, human; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D011991:Receptors, Virus; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: T-bet; Tim-3; gastric cancer; natural killer cells; tumor progression