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

Oncotarget. 2017 Mar 28;8(13):21794-21805. doi: 10.18632/oncotarget.15585.

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.

Keywords: prognostic factor; programmed cell death protein 1; programmed death-ligand 1; testicular germ cell tumors; tumor infiltrating lymphocytes.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / analysis*
  • Disease-Free Survival
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / immunology*
  • Neoplasms, Germ Cell and Embryonal / metabolism
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism
  • Proportional Hazards Models
  • Testicular Neoplasms / immunology*
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / mortality
  • Tissue Array Analysis
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor

Supplementary concepts

  • Testicular Germ Cell Tumor