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

• Published in: Oncotarget 2017-04, Vol.8 (16), p.26789-26801
• Main Authors: Ness, Nora, Andersen, Sigve, Khanehkenari, Mehrdad Rakaee, Nordbakken, Cecilie V, Valkov, Andrej, Paulsen, Erna-Elise, Nordby, Yngve, Bremnes, Roy M, Donnem, Tom, Busund, Lill-Tove, Richardsen, Elin
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; B7-H1 Antigen - metabolism; Basale medisinske, odontologiske og veterinærmedisinske fag: 710; Basic medical, dental and veterinary science disciplines: 710; Biomarkers, Tumor; Cancer-Associated Fibroblasts - metabolism; Humans; Immunohistochemistry; Immunomodulation; Immunophenotyping; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical disciplines: 700; Medical microbiology: 715; Medisinsk mikrobiologi: 715; Medisinske Fag: 700; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prognosis; Programmed Cell Death 1 Receptor - metabolism; Prostatic Neoplasms - immunology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Reproducibility of Results; Research Paper; Tissue Array Analysis; Tumor Burden; VDP
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.15817

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).