Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

// Michal Chovanec 1, 2, 7, * , Zuzana Cierna 3, * , Viera Miskovska 4 , Katarina Machalekova 5 , Daniela Svetlovska 2, 6 , Katarina Kalavska 2, 7, 8 , Katarina Rejlekova 1, 7 , Stanislav Spanik 4 , Karol Kajo 5 , Pavel Babal 3, 9 , Jozef Mardiak 1, 7 , Michal Mego 1, 2, 7 1 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic 2 Translational Research Unit, 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic 3 Department of Pathology, Comenius University, Faculty of Medicine, Bratislava, Slovak Republic 4 1st Department of Oncology, Comenius University, Faculty of Medicine & St. Elisabeth Cancer Institute, Bratislava, Slovak Republic 5 Department of Pathology, Slovak Medical University St. Elisabeth Cancer Institute, Bratislava, Slovak Republic 6 Department of Clinical Trials, National Cancer Institute, Bratislava, Slovak Republic 7 Department of Medical Oncology, National Cancer Institute, Bratislava, Slovak Republic 8 Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic 9 Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic * M-CH and Z-C share the first authorship Correspondence to: Michal Mego, email: misomego@gmail.com Keywords: programmed death-ligand 1, programmed cell death protein 1, tumor infiltrating lymphocytes, prognostic factor, testicular germ cell tumors Received: August 12, 2016     Accepted: January 10, 2017     Published: February 21, 2017 ABSTRACT Purpose: Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. Results: PD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with high infiltration of PD-L1 positive TILs (HS ≥ 160) had significantly better progression-free survival (HR = 0.17, 95% CI 0.09 – 0.31, p = 0.0006) and overall survival (HR = 0.08, 95% CI 0.04 – 0.16, p = 0.001) opposite to patients with lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in TGCTs. Materials and Methods: Surgical specimens from 240 patients with primary TGCTs were included into this translational study. The PD-1 and PD-L1 expression on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti-PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted histoscore (HS) method. Conclusions: The prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.