title: High tissue density of FOXP3+ T cells is associated with clinical outcome in prostate cancer.
abstract: Cell-mediated immunity may impact prostate cancer progression and has great therapeutic potential. Here, we investigated the clinical significance of the numeric density of regulatory T cells (Tregs) in prostate cancer as the presence of such cells in the tumour microenvironment has been linked to clinical outcome in other tumour entities. We detected Tregs by FOXP3 immunohistochemistry in 88.8% of 2002 prostate cancer specimens in tissue microarray format, the largest cohort so far in which Tregs have been quantified. The density of Tregs in tumour tissue was compared with pathological parameters and clinical outcome. The number of Tregs identified per 0.6mm tissue spot ranged from 1 to 10 in normal and 1 to 103 FOXP3+ cells in tumour samples. Prostate-specific antigen (PSA) recurrence-free survival was significantly reduced in patients with higher numbers of Tregs (p=0.0151). Further, a higher number of intratumoural FOXP3+ Tregs was associated with a more advanced tumour stage (p=0.0355) and higher Ki67 labelling index (p<0.0001). The tissue density of Tregs was unrelated to other clinical parameters such as spread to lymph nodes, preoperative PSA level and Gleason score. Our study suggests that the intratumoural presence of regulatory T cells may have substantial functional impact and may confer an adverse clinical course in prostate cancer.
authors.affiliation: Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Tumorzentrum (University Cancer Center Hamburg), Martinistrasse 52, 20246 Hamburg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Flammiger
authors.forename: Lars
authors.initials: L
authors.lastname: Weisbach
authors.forename: Hartwig
authors.initials: H
authors.lastname: Huland
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Martin
authors.initials: M
authors.lastname: Trepel
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D057234:Preoperative Period; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000276:immunology / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D000726:Androgen Antagonists; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D017430:Prostate-Specific Antigen