Abstract
PurposeTesticular 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.ResultsPD-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 MethodsSurgical 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.ConclusionsThe prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.
Highlights
Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies, most commonly found in young men [1]
This study aimed to evaluate the prognostic value of Programmed-death-1 receptor (PD-1) and PD-L1 expressing tumor infiltrating lymphocytes (TILs) in TGCTs
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)
Summary
Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies, most commonly found in young men [1]. Subsequent salvage chemotherapy may cure only 20-25% of patients with relapsed TGCTs [3,4,5]. The prognosis of patients who failed to be cured with conventional treatment is dismal. Our interest needs to be directed towards identification of predictive biomarkers and novel treatment strategies [6]. Malignant tumor biology and its’ associations with immune mechanisms have been recently a subject of intensified research. It occurs that immune check-point inhibition including PD-1, PD-L1 and/or CTLA4 is a highly effective modality in several types of malignancies [7,8,9,10]. Tumor infiltrating lymphocytes (TILs) are likewise proven to be an important biomarker with strong prognostic and predictive features in different types of tumors [11,12,13]
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