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Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors
Z Cierna1, M Mego2, V Miskovska3
1Department of Pathology, Faculty of Medicine.
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.
Insights
PD-L1 expression in testicular germ cell tumors (TGCTs) is linked to patient outcomes. Higher PD-L1 levels indicate a poorer prognosis, suggesting the PD-1/PD-L1 pathway as a potential therapeutic target for TGCTs.
Area of Science:
- Oncology
- Immunology
- Translational Research
Background:
- Testicular germ cell tumors (TGCTs) are highly chemosensitive, but some patients resist cisplatin-based chemotherapy.
- Immune checkpoint inhibitors targeting PD-1/PD-L1 pathways show promise in cancer therapy.
- Understanding PD-1 and PD-L1 roles in TGCTs is crucial for advancing treatment.
Purpose of the Study:
- To investigate the expression of PD-1 and PD-L1 in TGCTs.
- To determine the prognostic significance of PD-1 and PD-L1 in TGCT patients.
- To explore the PD-1/PD-L1 pathway as a potential therapeutic target in TGCTs.
Main Methods:
- Immunohistochemistry was used to detect PD-1 and PD-L1 expression in 140 TGCT surgical specimens.
- Expression levels were quantified using the quickscore (QS) method.
- Correlations were analyzed between PD-L1 expression, clinicopathological features, and patient survival outcomes.
Main Results:
- PD-L1 expression was significantly elevated in TGCTs compared to normal testicular tissue (mean QS 5.29 vs. 0.32, P < 0.0001).
- PD-L1 levels varied by subtype, with choriocarcinoma showing the highest expression.
- High PD-L1 expression correlated with adverse prognostic factors and poorer progression-free and overall survival.
Conclusions:
- PD-L1 expression serves as a significant prognostic biomarker in TGCTs.
- The PD-1/PD-L1 pathway represents a promising novel therapeutic target for TGCT treatment.
- Further research into PD-1/PD-L1 targeted therapies could improve outcomes for TGCT patients.
