Is PD-L1 a Prognostic Biomarker – and Potential Therapeutic Target – in Testicular GCTs?

December 23, 2015
Bryant Furlow
Bryant Furlow

Testicular germ cell tumor (TGCT) expression of the programmed cell death ligand 1 (PD-L1) might prove to be a prognostic biomarker, and blockade of the PD1/PD-L1 molecular pathway warrants investigation as a potential second-line treatment strategy for the minority of patients whose TGCTs prove to be refractory to standard first-line cisplatin-based chemotherapy.

Testicular germ cell tumor (TGCT) expression of the programmed cell death ligand 1 (PD-L1) might prove to be a prognostic biomarker, and blockade of the PD1/PD-L1 molecular pathway warrants investigation as a potential second-line treatment strategy for the minority of patients whose TGCTs prove to be refractory to standard first-line cisplatin-based chemotherapy, according to authors of a study published in the Annals of Oncology.

“In this translational study, we showed for the first time prognostic value of PD-L1 expression in TGCTs and our data imply that PD-1/PD-L1 pathway could be a novel therapeutic target in TGCTs,” concluded coauthors from Comenius University and the St. Elisabeth Cancer Institute in Bratislava, Slovak Republic.

The researchers studied programmed cell death protein 1 (PD-1) and PD-L1 expression in TGCT specimens from 140 patients (131 primary tumors and nine extragonadal GCTs). “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 to their expression in normal testicular tissue and correlated with clinicopathological characteristics and clinical outcome,” they explained.

Although no GCT samples expressed PD-1, “expression of PD-L1 was significantly higher in GCTs in comparison to normal testicular tissue (mean QS = 5.29 vs 0.32; P < .0001),” they reported. “Choriocarcinomas exhibit the highest level of PD-L1 with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and seminoma.”

PD-L1 expression was detected in 76% of seminomas and 89% of nonseminomas, they noted.

Tumors from patients with more advanced disease and poor prognostic features, including “≥ 3 metastatic sites, increased serum tumor markers, and/or nonpulmonary visceral metastases,” had higher expression levels of PD-L1, the researchers noted.

The researchers also found that patients with low PD-L1 expression experienced significantly better progression-free survival (PFS) and overall survival (OS) compared to patients with high PD-L1 expression (PFS hazard ratio [HR] 0.40, 95% CI:0.16 - 1.01; P = .008; OS HR 0.43, 95% CI:0.15 - 1.23; P = .040). “The highest PD-L1 expression was found in choriocarcinomas, with decreasing positivity in embryonal carcinoma, teratoma, yolk sac tumor and the lowest expression in seminoma,” the researchers reported. “When we evaluated dichotomized PD-L1 expression, only 20 % of TGCTs had high PD-L1 expression (QS ≥ 10), while none of the normal testicular tissue exhibit high PD-L1 expression. Embryonal carcinoma had significantly higher expression compared to seminoma and yolk sac tumors (P < .01), while choriocarcinomas had significantly higher PD-L1 overexpression when compared to all other histological subtypes (P < .001).”

“Based on these data we suggest that PD- 1/PD-L1 is a novel promising therapeutic target for poor prognosis and/or multiple relapsed/refractory TGCTs,” they concluded.

Study limitations included its “retrospective nature” and the relative underrepresentation of choriocarcinoma, yolk sac tumor, and extragonadal GCTs, the coauthors reported. TGCT PD-L1 expression was associated with expression levels in normal adjacent testicular tissue, but was still higher in tumor tissue, they noted.