title: Cancerous HLA class I expression and regulatory T cell infiltration in gastric cancer.
abstract: BACKGROUND
  Since antitumor immune reactions between tumors and intratumoral immunocytes have been verified in several human tumors, immunological therapeutic strategies must be considered to obtain the proper efficacy of tumor shrinkage under these conditions. Human leukocyte antigen (HLA) class I expression in cancer cells and degree of infiltration of regulatory T cells (Tregs) in the stroma have been regarded as important markers of antitumor immune reactions in the context of independent immunological mechanisms. In the current study, we investigated HLA class I expression and Treg cells infiltration in gastric cancer and discussed the clinical implications of this combinatory analysis in gastric cancer.
  
  
  METHODS
  A total of 141 gastric cancer patients who received R0 gastrectomy at Kagoshima University Hospital were studied. Immunohistochemically, in 141 gastric cancer patients, HLA class I expression and Treg cell infiltration in cancerous tissue were evaluated using HLA class I (EMR8-5) and forkhead box p3 (FOXP3) monoclonal antibodies. The correlation between clinical factors and tumor-infiltrating Treg cells was analyzed.
  
  
  RESULTS
  HLA class I expression was positively associated with depth of tumor invasion (P < 0.05). Infiltration of Foxp3-positive cells did not correlate with any clinicopathological markers. HLA class I expression had no association with Treg cell infiltration (r = 0.04). A better postoperative outcome was associated with fewer numbers of Treg infiltration (P = 0.034). A combination of HLA and Treg analysis may lead to a more accurate prediction of postoperative outcome (P = 0.02).
  
  
  CONCLUSIONS
  Two different antitumor immunological markers, Treg infiltration and HLA class I expression, affected clinicopathological factors in gastric cancer by different mechanisms. Thus, an immunological combination of HLA class I expression and Treg cell infiltration may more accurately predict postoperative outcome. Immunological balance needs to be restored after evaluation of each immunological deficit in gastric cancer.
authors.affiliation: Department of Digestive Surgery, and Breast and Thyroid Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. ishiga@m.kufm.kagoshima-u.ac.jp
authors.forename: Sumiya
authors.initials: S
authors.lastname: Ishigami
authors.forename: Takaaki
authors.initials: T
authors.lastname: Arigami
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Uenosono
authors.forename: Masataka
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okumura
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Uchikado
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kita
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nishizono
authors.forename: Kosei
authors.initials: K
authors.lastname: Maemura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kijima
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakajo
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Owaki
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ueno
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hokita
authors.forename: Shoji
authors.initials: S
authors.lastname: Natsugoe
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D005743:Gastrectomy / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015395:Histocompatibility Antigens Class I