Oncotarget

Research Papers:

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

Michal Chovanec _, Zuzana Cierna, Viera Miskovska, Katarina Machalekova, Daniela Svetlovska, Katarina Kalavska, Katarina Rejlekova, Stanislav Spanik, Karol Kajo, Pavel Babal, Jozef Mardiak and Michal Mego

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Oncotarget. 2017; 8:21794-21805. https://doi.org/10.18632/oncotarget.15585

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Abstract

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

Correspondence to:

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

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.


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