Prognostic Value of Programmed-Death-1 Receptor (PD-1) and Its Ligand 1 (PD-L1) in Testicular Germ Cell Tumors
Open accessAbstract
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.
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PD-L1 is overexpressed in patients with GCN (76% of seminomas and 89% of non-seminomas) compared to normal testicular tissue.
“PD-L1 is overexpressed in patients with GCN (76% of seminomas and 89% of non-seminomas) compared to normal testicular tissue [24].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [24]
Low PD-L1 expression is associated with longer PFS and OS.
“High PD-L1 expression is a harbinger of poor prognostic features, including non-seminomatous histology, increased number of metastatic sites, high serum tumor markers and the presence non-pulmonary visceral metastases, whereas low PD-L1 expression is associated with longer PFS and OS [24].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [24]
High PD-L1 expression is associated with poor prognostic features, including non-seminomatous histology, increased number of metastatic sites, high serum tumor markers, and presence of non-pulmonary visceral metastases.
“High PD-L1 expression is a harbinger of poor prognostic features, including non-seminomatous histology, increased number of metastatic sites, high serum tumor markers and the presence non-pulmonary visceral metastases, whereas low PD-L1 expression is associated with longer PFS and OS [24].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [24]
PD-L1 overexpression is most pronounced in choriocarcinomas, decreased in embryonal carcinoma, teratoma and yolk sack tumors, and lowest in seminomas.
“With regard to histological subtypes, PD-L1 overexpression was found to be most pronounced in patients with choriocarcinomas, while decreased in embryonal carcinoma, teratoma and yolk sack tumors, with the lowest expression observed in seminomas [24].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [24]
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- Authors
- Cierna, Z., Mego, M., Miskovska, V., Machalekova, K., Chovanec, M., Svetlovska, D., Hainova, K., Rejlekova, K., Macak, D., Spanik, S., Ondrus, D., Kajo, K., Mardiak, J., & Babal, P.
- Affiliations
- National Cancer Institute (UA)
- Slovak Academy of Sciences (SK)
- Slovak Medical University (SK)
- Corresponding author
- Mego, M.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2016-02
- Volume
- 27
- Issue
- 2
- Pages
- 300-305
- ISSN
- 0923-7534 (ISSN-L)
- PMC
- PMC4751222
- OpenAlex
- W2172770673
- Cited by
- 162
- References
- 28
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 24 · 2023: 14 · 2022: 12 · 2021: 12 · 2020: 21 · 2019: 15 · 2018: 21 · 2017: 16 · 2016: 10 · 2015: 2
- FWCI
- 16.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Slovak Research and Development Agency (APVV-0016-11)
- Topics
- Health Sciences › Medicine › Surgery › Testicular diseases and treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- testicular germ cell tumors, PD-1, PD-L1, PD-1/PD-L1 pathway, prognostic factors, choriocarcinoma, embryonal carcinoma, teratoma, yolk sac tumor, seminoma, progression-free survival, overall survival, metastasis, serum tumor markers, immunotherapy targets
- MeSH terms
- Adolescent, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Choriocarcinoma, Cisplatin, Humans, Immunotherapy, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal, Testicular Neoplasms, Biomarkers, Tumor, Disease-Free Survival, Young Adult, Translational Research, Biomedical, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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