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
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Nora Ness1, Sigve Andersen2,3, Mehrdad Rakaee Khanehkenari1, Cecilie V. Nordbakken4, Andrej Valkov4, Erna-Elise Paulsen2,3, Yngve Nordby2,5, Roy M. Bremnes2,3, Tom Donnem2,3, Lill-Tove Busund1,4, Elin Richardsen1,4
1Department of Medical Biology, UiT The Arctic University of Norway, N-9037 Tromso, Norway
2Department of Clinical Medicine, UiT The Arctic University of Norway, N-9037 Tromso, Norway
3Department of Oncology, University Hospital of North Norway, N-9038 Tromso, Norway
4Department of Clinical Pathology, University Hospital of North Norway, N-9038 Tromso, Norway
5Department of Urology, University Hospital of North Norway, N-9038 Tromso, Norway
Nora Ness, email: firstname.lastname@example.org
Keywords: prostate cancer, PDL-1, PD-1, immunohistochemistry, prognostic marker
Received: May 27, 2016 Accepted: February 20, 2017 Published: March 01, 2017
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 < 65, preoperative PSA > 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).
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