Immune Checkpoint Expression in Orbitally Invasive Sinonasal Undifferentiated Carcinoma: Implications for Therapeutic Manipulation.

PURPOSE: The objective of this study is to investigate whether checkpoint inhibitor proteins, including programed death protein-1, programmed death-1-pathway ligand, cytotoxic T-lymphocyte associated protein-4, lymphocyte activation gene-3, and CD73, are implicated in orbitally invasive sinonasal undifferentiated carcinomas (SNUCs). METHODS: Patients with orbitally invasive SNUC presenting to a single institution between 2020 and 2024 were identified. Age and gender match controls were identified. Immunohistochemical staining was performed for each of the checkpoint inhibitors. Using light microscopy, the number of positively staining cells per 40× field was recorded across 5 consecutive fields and averaged. The differences in expression between the 2 were compared via a Mann-Whitney analysis. RESULTS: Six patients with orbitally invasive SNUC and 11 sinus mucosal controls were identified. Immunohistochemical analysis of these tumors demonstrated positivity in both SNUC specimen and normal sinus mucosa for all biomarkers tested (CD73, lymphocyte activation gene-3, cytotoxic T-lymphocyte associated protein-4, programmed death-1-pathway ligand, programed death protein-1). Expression of CD73 and programmed death-1-pathway ligand was statistically significantly higher in SNUC specimens compared with normal sinus controls (p = 0.0003 and p = 0.0111, respectively). CONCLUSION: Specimens from patients with sinonasal undifferentiated carcinoma express increased levels of programmed death-1-pathway ligand and CD73 compared with sinus controls. The results discovered in this investigation represent a significant proof of principle that immunotherapy may be a promising approach to address a potentially devastating disease.