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

Area of Science:

• Oncology
• Immunology
• Head and Neck Surgery

Background:

• Sinonasal undifferentiated carcinoma (SNUC) is an aggressive malignancy.
• The role of immune checkpoint proteins in SNUC is not well understood.
• Orbitally invasive SNUC presents unique challenges in treatment and prognosis.

Purpose of the Study:

• To investigate the expression of key checkpoint inhibitor proteins in orbitally invasive SNUC.
• To compare checkpoint protein expression in SNUC tumors versus normal sinus mucosa.
• To determine if specific checkpoint proteins are implicated in the pathogenesis of SNUC.

Main Methods:

• Retrospective identification of patients with orbitally invasive SNUC and age/gender-matched controls.
• Immunohistochemical staining for programed death protein-1 (PD-1), programmed death-1-pathway ligand (PD-L1), cytotoxic T-lymphocyte associated protein-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and CD73.
• Quantitative analysis of protein expression using light microscopy.
• Statistical comparison of expression levels between SNUC and control groups using the Mann-Whitney test.

Main Results:

• Immunohistochemical analysis revealed positivity for all tested checkpoint inhibitors in both SNUC and normal sinus mucosa.
• Expression of CD73 and PD-L1 was significantly higher in SNUC specimens compared to normal sinus controls (p = 0.0003 and p = 0.0111, respectively).
• No significant difference was observed for PD-1, CTLA-4, or LAG-3 expression between the groups.

Conclusions:

• Patients with SNUC exhibit increased expression of PD-L1 and CD73 compared to sinus controls.
• These findings provide a proof of principle for the potential efficacy of immunotherapy in treating SNUC.
• Targeting PD-L1 and CD73 pathways may represent a novel therapeutic strategy for this devastating disease.