title: The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer.
abstract: BACKGROUND
  Intratumoural lymphocytic infiltration is strongly associated with the outcome of many human epithelial cancers. The current paper investigated whether subpopulations of tumour-infiltrating T lymphocytes are associated with certain clinicopathological parameters and the prognosis of patients with invasive bladder cancer (BCa).
  
  
  METHODS
  The infiltration densities of the adaptive immune markers CD3 (the whole T cell population), FOXP3 (regulatory T cells; Tregs), CD8 (T effector cells) and CD45R0 (T effector memory cells) were analysed by immunohistochemistry and image analysis with tissue microarrays of tumour tissues from 149 patients with invasive BCa treated with radical cystectomy. The findings were correlated with certain clinicopathological parameters.
  
  
  RESULTS
  Higher FOXP3/CD3 [OS: p = 0.016, HR 1.29, 95% confidence intervals (95% CIs 1.05-1.59)] and FOXP3/CD8 (OS: p = 0.013, HR 1.32, 95% CIs 1.06-1.65) ratios were significantly associated with briefer overall survival and time to cancer-specific death; the latter ratio represented an independent prognostic factor according to a multivariate analysis adjusted for pathological T and N stages (HR 1.32, 95% CIs 1.05-1.67, p = 0.018). The infiltration densities of individual markers (CD3, CD8, FOXP3 and CD45R0) were not significantly associated with clinicopathological parameters or survival; however, a trend towards a better outcome was observed for higher log-transformed CD8 (p = 0.070, HR 0.80, 95% CIs 0.63-1.02) and CD3 (p = 0.113, HR 0.84, 95% CIs 0.68-1.04) infiltration values.
  
  
  CONCLUSIONS
  A high fraction of Tregs amongst CD3- and CD8-positive lymphocytes indicated a poor prognosis, thereby emphasising the important role that Tregs play in the suppression of the anti-tumour immune response. No single lymphocytic marker was significantly correlated with clinical outcomes, but high CD3 and CD8 infiltration showed trends towards better prognosis.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. t.horn@lrz.tum.de.|Urologische Klinik und Poliklinik der Technischen Universität München, Ismaningerstraße 22, 81675, Munich, Germany. t.horn@lrz.tum.de.
authors.forename: T
authors.initials: T
authors.lastname: Horn
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Laus
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Seitz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: S C
authors.initials: SC
authors.lastname: Schmid
authors.affiliation: Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Wolf
authors.affiliation: Institute of Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Haller
authors.affiliation: Institute for Pathology and Pathological Anatomy, Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Winkler
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Nawroth
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: J E
authors.initials: JE
authors.lastname: Gschwend
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: H R
authors.initials: HR
authors.lastname: Kübler
authors.affiliation: Institute for Pathology and Pathological Anatomy, Technische Universität München, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Slotta-Huspenina
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology*; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology
keywords: Bladder cancer; Lymphocyte; Prognosis; Regulatory T cell