title: Expression of Forkhead box P3 in tumour cells causes immunoregulatory function                     of signet ring cell carcinoma of the stomach.
abstract: BACKGROUND
  It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma.
  
  
  METHODS
  We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines.
  
  
  RESULTS
  Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-β augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown.
  
  
  CONCLUSIONS
  Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma.
authors.affiliation: Department of Surgical Oncology,                         Osaka City University Graduate School of Medicine, 1-4-3,                         Asahi-machi, Abeno-ku, Osaka                     545-8585, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yoshii
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Ohira
authors.forename: K
authors.initials: K
authors.lastname: Muguruma
authors.forename: T
authors.initials: T
authors.lastname: Iwauchi
authors.forename: T
authors.initials: T
authors.lastname: Lee
authors.forename: K
authors.initials: K
authors.lastname: Sakurai
authors.forename: N
authors.initials: N
authors.lastname: Kubo
authors.forename: M
authors.initials: M
authors.lastname: Yashiro
authors.forename: T
authors.initials: T
authors.lastname: Sawada
authors.forename: K
authors.initials: K
authors.lastname: Hirakawa
mesh_terms: D018279:Carcinoma, Signet Ring Cell / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D007150:Immunohistochemistry; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger