title: Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors.
abstract: BACKGROUND
  Testicular germ cell tumors (TGCTs) belong to the most chemosensitive solid tumors; however, a small proportion of patients fail to be cured with cisplatin-based chemotherapy. Inhibitors of PD-1/PD-L1 pathways represent a new class of promising drugs in anticancer therapy. The aim of this study was to evaluate expression and prognostic value of PD-1 and PD-L1 in TGCTs.
  
  
  METHODS
  Surgical specimens from 140 patients with TGCTs (131 with primary testicular tumor and 9 with extragonadal GCTs) were included into the translational study. PD-1 and PD-L1 expression was detected in the tumor tissue by immunohistochemistry using monoclonal antibodies, scored by the multiplicative quickscore (QS) method, compared with their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome.
  
  
  RESULTS
  None of the GCTs exhibited PD-1 protein, although expression of PD-L1 was significantly higher in GCTs in comparison with normal testicular tissue (mean QS = 5.29 versus 0.32, P < 0.0001). Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma. PD-L1 expression was associated with poor prognostic features, including ≥3 metastatic sites, increased serum tumor markers and/or non-pulmonary visceral metastases. Patients with low PD-L1 expression had significantly better progression-free survival [hazard ratio (HR) = 0.40, 95% confidence interval (CI) 0.16-1.01, P = 0.008] and overall survival (HR = 0.43, 95% CI 0.15-1.23, P = 0.040) compared with patients with high PD-L1 expression.
  
  
  CONCLUSIONS
  In this translational study, we showed, for the first time, the prognostic value of PD-L1 expression in TGCTs and our data imply that the PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs.
authors.affiliation: Department of Pathology, Faculty of Medicine.
authors.forename: Z
authors.initials: Z
authors.lastname: Cierna
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava misomego@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Mego
authors.affiliation: Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
authors.forename: V
authors.initials: V
authors.lastname: Miskovska
authors.affiliation: Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
authors.forename: K
authors.initials: K
authors.lastname: Machalekova
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
authors.forename: M
authors.initials: M
authors.lastname: Chovanec
authors.affiliation: Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute.
authors.forename: D
authors.initials: D
authors.lastname: Svetlovska
authors.affiliation: Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Cancer Research Institute, Slovak, Academy of Sciences, Bratislava.
authors.forename: K
authors.initials: K
authors.lastname: Hainova
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
authors.forename: K
authors.initials: K
authors.lastname: Rejlekova
authors.affiliation: Department of Pathology, National Cancer Institute, Bratislava.
authors.forename: D
authors.initials: D
authors.lastname: Macak
authors.affiliation: Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
authors.forename: S
authors.initials: S
authors.lastname: Spanik
authors.affiliation: Faculty of Medicine, St Elisabeth Cancer Institute, Bratislava.
authors.forename: D
authors.initials: D
authors.lastname: Ondrus
authors.affiliation: Department of Pathology, Slovak Medical University and St Elisabeth Cancer Institute, Bratislava.
authors.forename: K
authors.initials: K
authors.lastname: Kajo
authors.affiliation: 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute Translational Research Unit, 2nd Department of Oncology, Faculty of Medicine and National Cancer Institute 1st Department of Oncology, Comenius University, Bratislava.
authors.forename: J
authors.initials: J
authors.lastname: Mardiak
authors.affiliation: Department of Pathology, Faculty of Medicine Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic.
authors.forename: P
authors.initials: P
authors.lastname: Babal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood*; D002822:Choriocarcinoma / Q000473:pathology*; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology*; D057170:Translational Research, Biomedical; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D002945:Cisplatin
keywords: immunotherapy; prognosis; programmed death receptor 1; programmed death-ligand 1; testicular germ cell tumors