The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) in a large, multicenter prostate cancer cohort

// Nora Ness 1 , Sigve Andersen 2, 3 , Mehrdad Rakaee Khanehkenari 1 , Cecilie V. Nordbakken 4 , Andrej Valkov 4 , Erna-Elise Paulsen 2, 3 , Yngve Nordby 2, 5 , Roy M. Bremnes 2, 3 , Tom Donnem 2, 3 , Lill-Tove Busund 1, 4 , Elin Richardsen 1, 4 1 Department of Medical Biology, UiT The Arctic University of Norway, N-9037 Tromso, Norway 2 Department of Clinical Medicine, UiT The Arctic University of Norway, N-9037 Tromso, Norway 3 Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway 4 Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromso, Norway 5 Department of Urology, University Hospital of North Norway, N-9038 Tromso, Norway Correspondence to: Nora Ness, email: nora.ness4@gmail.com Keywords: prostate cancer, PDL-1, PD-1, immunohistochemistry, prognostic marker Received: May 27, 2016      Accepted: February 20, 2017      Published: March 01, 2017 ABSTRACT Programmed cell death protein 1 (PD-1) and its ligand Programmed death ligand 1 (PD-L1) have gained massive attention in cancer research due to recent availability and their targeted antitumor effects. Their role in prostate cancer is still undetermined. We constructed tissue microarrays from prostatectomy specimens from 535 prostate cancer patients. Following validation of antibodies, immunohistochemistry was used to evaluate the expression of PD-1 in lymphocytes and PD-L1 in epithelial and stromal cells of primary tumors. PD-L1 expression was commonly seen in tumor epithelial cells (92% of cases). Univariate survival analysis revealed a positive association between a high density of PD-1+ lymphocytes and worse clinical failure-free survival, limited to a trend ( p = 0.084). In subgroups known to indicate unfavorable prostate cancer prognosis (Gleason grade 9, age 10, pT3) patients with high density of PD-1+ lymphocytes had a significantly higher risk of clinical failure ( p = < 0.001, p = 0.025, p = 0.039 and p = 0.011, respectively). In the multivariate analysis, high density of PD-1+ lymphocytes was a significant negative independent prognostic factor for clinical failure-free survival (HR = 2.48, CI 95% 1.12–5.48, p = 0.025).