title: Increased prevalence of tumor-infiltrating regulatory T cells is closely related to their lower sensitivity to H2O2-induced apoptosis in gastric and esophageal cancer.
abstract: OBJECTIVE
  Although an increase in regulatory T cells (Tregs) is observed in tumor microenvironments, the underlying mechanism is not fully clarified. Since it was suggested that Tregs showed a lower sensitivity toward oxidative stress in comparison with conventional T cells, in the present study, we investigated the H(2)O(2) production and apoptosis of Tregs in gastric and esophageal cancer tissues, employing flow cytometric analysis using fresh samples (n = 93) and immunohistochemical analysis (n = 203).
  
  
  RESULTS
  The increased tumor-infiltrating Tregs coexisted with elevated H(2)O(2) production according to disease progression. The grade of apoptosis in Tregs was less pronounced than that in conventional T cells, and there was a positive correlation between H(2)O(2) production and the grade of apoptosis in conventional T cells, while there was no correlation between H(2)O(2) production and the grade of apoptosis in Tregs. Moreover, Tregs were less sensitive to H(2)O(2)-induced apoptosis compared with conventional T cells in vitro.
  
  
  CONCLUSIONS
  We have demonstrated that the increased prevalence of tumor-infiltrating Tregs closely related to their lower sensitivity to H(2)O(2)-induced apoptosis.
authors.affiliation: First Department of Surgery, University of Yamanashi, Kofu and Tamaho, Japan.
authors.forename: Shinichirou
authors.initials: S
authors.lastname: Izawa
authors.forename: Kousaku
authors.initials: K
authors.lastname: Mimura
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Takanori
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Koji
authors.initials: K
authors.lastname: Kono
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D016877:Oxidants; D006861:Hydrogen Peroxide