Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors

Autor: Michal Mego, Daniela Svetlovska, Dalibor Ondrus, Michal Chovanec, Katarina Rejlekova, Stanislav Spanik, Katarina Hainova, Zuzana Cierna, Jozef Mardiak, Dusan Macak, Katarina Machalekova, Karol Kajo, Viera Miskovska, Pavel Babal
Rok vydání: 2016
Předmět:
Oncology
Male
0301 basic medicine
Pathology
medicine.medical_treatment
Programmed Cell Death 1 Receptor
030232 urology & nephrology
B7-H1 Antigen
Translational Research
Biomedical
0302 clinical medicine
Medicine
Choriocarcinoma
Receptor
biology
Antibodies
Monoclonal
Hematology
Middle Aged
Neoplasms
Germ Cell and Embryonal
Prognosis
Ligand (biochemistry)
030220 oncology & carcinogenesis
Immunohistochemistry
Immunotherapy
Teratoma
medicine.drug
Adult
endocrine system
medicine.medical_specialty
Adolescent
Urology
Antineoplastic Agents
Disease-Free Survival
Embryonal carcinoma
Young Adult
03 medical and health sciences
Testicular Neoplasms
Internal medicine
PD-L1
Biomarkers
Tumor
Humans
Progression-free survival
Aged
Cisplatin
Chemotherapy
business.industry
Original Articles
Seminoma
medicine.disease
Testicular germ cell
030104 developmental biology
Cancer research
biology.protein
Programmed death 1
business
Zdroj: Annals of Oncology. 27:300-305
ISSN: 0923-7534
Popis: 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. PATIENTS AND 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.
Databáze: OpenAIRE
Externí odkaz: