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Immune Checkpoint Expression in Orbitally Invasive Sinonasal Undifferentiated Carcinoma: Implications for Therapeutic
Carisa E Bohnak1, Jordon G Grube2, Nada Farhat3
1Department of Ophthalmology, Lions Eye Institute.
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.
Insights
Checkpoint inhibitors programmed death-1-pathway ligand and CD73 are elevated in sinonasal undifferentiated carcinoma (SNUC). This suggests immunotherapy may offer a promising treatment for this aggressive cancer.
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.
