title: The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer.
abstract: OBJECTIVE
  Therapies targeting the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway promote anti-tumor immunity and have shown promising results in various tumors. Preliminary data further indicate that immunohistochemically detected PD-L1 may be predictive for anti-PD-1 therapy. So far, no data are available on PD-L1 expression in primary prostate cancer.
  
  
  METHODS
  Following validation of a monoclonal antibody, immunohistochemical analysis of PD-L1 expression was performed in two independent, well-characterized cohorts of primary prostate cancer patients following radical prostatectomy (RP), and resulting data were correlated to clinicopathological parameters and outcome.
  
  
  RESULTS
  In the training cohort (n= 209), 52.2% of cases expressed moderate to high PD-L1 levels, which positively correlated with proliferation (Ki-67,P< 0.001), Gleason score (P= 0.004), and androgen receptor (AR) expression (P< 0.001). Furthermore, PD-L1 positivity was prognostic for biochemical recurrence [BCR;P= 0.004; HR, 2.37; 95% confidence interval (CI), 1.32-4.25]. In the test cohort (n= 611), moderate to high PD-L1 expression was detected in 61.7% and remained prognostic for BCR in univariate Cox analysis (P= 0.011; HR, 1.49; 95% CI, 1.10-2.02). The correlation of Ki-67 and AR with PD-L1 expression was confirmed in the test cohort (P< 0.001). In multivariate Cox analysis of all patients, PD-L1 was corroborated as independently prognostic for BCR (P= 0.007; HR, 1.46; 95% CI, 1.11-1.92).
  
  
  CONCLUSIONS
  We provide first evidence that expression of the therapy target PD-L1 is not only highly prevalent in primary prostate cancer cells but is also an independent indicator of BCR, suggesting a biologic relevance in primary tumors. Further studies need to ascertain if PD-1/PD-L1-targeted therapy might be a treatment option for hormone-naïve prostate cancers.
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Gevensleben
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Dimo
authors.initials: D
authors.lastname: Dietrich
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Golletz
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Steiner
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Jung
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Thore
authors.initials: T
authors.lastname: Thiesler
authors.affiliation: Institute of Dermatopathology, Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Majores
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stein
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Uhl
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Urology, University Hospital Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.affiliation: Department of Urology, Charité University Hospital Berlin, Berlin, Germany. Berlin Institute for Urologic Research, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.affiliation: Department of Urology, Charité University Hospital Berlin, Berlin, Germany. Berlin Institute for Urologic Research, Berlin, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.affiliation: Department of Hematology and Oncology, University Hospital Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Institute of Pathology, University Hospital Bonn, Bonn, Germany. Glen.Kristiansen@ukb.uni-bonn.de.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D056747:Immunomodulation; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D063868:Patient Outcome Assessment; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor