title: Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer.
abstract: OBJECTIVE
  Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer.
  
  
  METHODS
  Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained. We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test.
  
  
  RESULTS
  HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I-positive tumors and those with HLA class I-negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects.
  
  
  CONCLUSIONS
  Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan. hkitamu@sapmed.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Ichiya
authors.initials: I
authors.lastname: Honma
authors.forename: Eiji
authors.initials: E
authors.lastname: Sato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D015395:Histocompatibility Antigens Class I