title: T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept.
abstract: OBJECTIVE
  To define immunoscore in bladder cancer studying T helper 1 (Th1) immunoreaction. To define a cancer-specific survival model based on Th1 cells infiltration.
  
  
  METHODS
  A total of 252 patients underwent primary transurethral resection of bladder tumour at our Institution. A retrospective review of a selected cohort with pT1 and muscle-invasive bladder cancer (MIBC) lesions was performed. Pathology blocks were marked with CD3 and CD8 antibodies. Immune cells density in stromal reaction (SR) was measured on five distinct high-power field (HPF) by two dedicated uro-pathologist blinded for patients' evolution.
  
  
  METHODS
  Student test or non-parametric Wilcoxon test as appropriate to compare means between two groups. Receiver operating characteristics (ROC) curve to define markers threshold. Cox model to assess survival's predictors.
  
  
  RESULTS
  Ten pT1 and 20 MIBC consecutive cases were analysed. Median follow-up was 33.4 months. Immunohistological analysis for pT1 lesions featured limited SR. For MIBC, the mean density of lymphocytes in the SR was of 105/HPF (CD3) and 86/HPF (CD8). Survivors harboured higher lymphocytes densities versus non survivors (CD3: p = 0.0319; CD8: p = 0.0279). CD3 (p = 0.034) and CD8 (p = 0.034) lymphocytes densities were independently associated with cancer-specific survival on Cox model analyses. The retrospective design and small size of cohorts are the study limitations.
  
  
  CONCLUSIONS
  High CD3 and CD8 lymphocytes SR densities are associated with better cancer-specific survival for MIBC. Th1 reaction against the tumour seems to be protective for bladder cancer. Further evaluation is warranted.
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ingels
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Rafael E
authors.initials: RE
authors.lastname: Sanchez Salas
authors.affiliation: Hôpital Bichat, Department of Urology, 46 Rue Henri Huchard, 75018 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Ravery
authors.affiliation: Hôpital Bretonneau, Department of Pathology, 2 Boulevard Tonnelé, 37000 Tours, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Fromont-Hankard
authors.affiliation: Institut Montsouris, Department of Pathology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.affiliation: Hôpital Bicêtre, Department of Urology, 78 Rue du Général Leclerc, 94270 le Kremlin-Bicêtre, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.affiliation: Hôpital Bicêtre, Department of Urology, 78 Rue du Général Leclerc, 94270 le Kremlin-Bicêtre, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Pignot
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Prapotnich
authors.affiliation: ALTRAN, Department of Statistics, 2 Rue Paul Dautier, 78140 Véllizy-Villacoublay, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Olivier
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Galiano
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Barret
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Rozet
authors.affiliation: Institut Montsouris, Department of Pathology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Weber
authors.affiliation: Institut Montsouris, Department of Urology, 42 Boulevard Jourdan, 75014 Paris, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cathelineau
keywords: bladder cancer; immune reaction; immunohistochemistry; immunoscore; markers; prognosis; tumor infiltrating lympocytes