Expression of Programmed Cell Death-Ligand 1 in Esthesioneuroblastoma

Background Programmed death-ligand 1 (PD-L1) is a transmembrane glycoprotein which interacts with the receptor programmed death 1 (PD-1) to suppress T-cell signaling, increase tolerance to self-antigens, and promote tumor immune evasion. There has been significant recent interest in the chemotherapeutic use of immune checkpoint inhibitors including the PD-L1/PD-1 pathway due to significant efficacy observed in melanoma and non-small cell lung cancer. These inhibitors are believed to act through reinvigoration of tumor-associated CD8+ T cells. Preclinical studies with glioma cells in mice treated with anti-PD-1 treatment combined with radiation have shown promise and numerous clinical trials are actively investigating PD-L1/PD-1 blockade in malignant glioma and recurrent glioblastoma. Despite these advances, the expression of the PD-L1/PD-1 pathway in esthesioneuroblastoma (ENB) has yet to be investigated. The goal of this study was to determine the expression pattern of PD-L1 and PD-1 in ENB and to determine the presence of CD8+ cells in PD-L1 expressing tumors.

Methods Immunohistochemical analysis for expression of PD-L1 was performed on a total of 10 available samples of ENB. Tumors expressing PD-L1 underwent further immunohistochemistry analysis to determine the expression of PD-1 as well as the presence of tumor-associated CD8+ cells. A review of clinical records from these 10 samples was performed.

Results Three of the ten ENB specimens demonstrated significant positive PD-L1 expression. Two of the PD-L1-positive tumors were available for additional immunohistochemical analysis. Both specimens demonstrated the presence of CD8+ cells and the highest PD-L1 expressing specimen demonstrated 75% coexpression of PD-1. Further analysis of PD-L1 expressing ENB did not demonstrate a correlation between PD-L1 expression and Kadish stage or Hyams grade.

Conclusion These expression data suggest that a significant number of ENBs express PD-L1 and have an associated infiltrate of CD8+ cells. Future studies are necessary to assess the potential for effectiveness of PD-L1/PD-1 inhibitors in ENB.