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

Abstract

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