Expression of Programmed Cell Death Ligand 1 and Associated Lymphocyte Infiltration in Olfactory Neuroblastoma

Abstract

Background: Programmed cell death ligand 1 (PD-L1) is a transmembrane glycoprotein that interacts with the receptor programmed cell death 1 (PD-1) to suppress T-cell activation, reduce adjacent tissue damage, and promote tolerance to self-antigens. Tumors may express PD-L1 as a mechanism to evade immune detection. Recent clinical trials have demonstrated the efficacy of PD-L1/PD-1 antagonists through activation of tumor-infiltrated CD8⁺ T cells. The aim of this study was to determine the expression pattern of PD-L1 and PD-1 in olfactory neuroblastoma (ONB) tumor cells and to determine the presence of PD-1⁺ and CD8⁺ lymphocytes in the ONB immune microenvironment.

Methods: Immunohistochemistry for expression of PD-L1, PD-1, and CD8 was performed on paraffin-embedded ONB tissue.

Results: Of the 10 primary site ONB samples, 4 demonstrated positive PD-L1 expression. Of PD-L1⁺ tumors, the 2 highest expressing samples were found to contain PD-1⁺ tumor cells. Of the 4 available metastatic samples, all of which arose from PD-L1^- primary site ONB, 3 were positive for PD-L1 and contained PD-1⁺ tumor cells. PD-L1⁺ primary and metastatic tumors also demonstrated increased PD-1⁺ infiltrating lymphocytes in the tumor and stroma (11.6- and 4.62-fold increase) compared with PD-L1^- samples (P < 0.05 and P = 0.068 respectively). PD-L1⁺ specimens demonstrated increased CD8⁺ lymphocytes in the tumor and stroma (7.46- and 2.14-fold increase) compared with PD-L1^- tumors (P < 0.05 for both).

Conclusions: These data demonstrate that a proportion of ONB primary and metastatic tumors express PD-L1 and possess an associated tumor and stromal infiltrate of PD-1⁺ and CD8⁺ lymphocytes.

Keywords: Esthesioneuroblastoma; Immune checkpoint inhibitors; Immunotherapy; Olfactory neuroblastoma; PD-L1.