Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors
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Michal Chovanec1,2,7,*, Zuzana Cierna3,*, Viera Miskovska4, Katarina Machalekova5, Daniela Svetlovska2,6, Katarina Kalavska2,7,8, Katarina Rejlekova1,7, Stanislav Spanik4, Karol Kajo5, Pavel Babal3,9, Jozef Mardiak1,7, Michal Mego1,2,7
12nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic
2Translational Research Unit, 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic
3Department of Pathology, Comenius University, Faculty of Medicine, Bratislava, Slovak Republic
41st Department of Oncology, Comenius University, Faculty of Medicine & St. Elisabeth Cancer Institute, Bratislava, Slovak Republic
5Department of Pathology, Slovak Medical University St. Elisabeth Cancer Institute, Bratislava, Slovak Republic
6Department of Clinical Trials, National Cancer Institute, Bratislava, Slovak Republic
7Department of Medical Oncology, National Cancer Institute, Bratislava, Slovak Republic
8Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic
9Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic
*M-CH and Z-C share the first authorship
Michal Mego, email: [email protected]
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
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.
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