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Biomarkers for Immunotherapy in Poorly Differentiated Sinonasal Tumors
Eva Villanueva-Fernández1, Mario A Hermsen2, Laura Suárez-Fernández2
1Department Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain.
Abstract:
The sinonasal cavities harbor a wide variety of rare cancer types. Histopathological classification can be challenging, especially for poorly differentiated tumors. Despite advances in surgery and radio-chemotherapy, the 5-year survival rate is still very low. Thus, there is an unmet clinical need for new therapeutic options. We retrospectively evaluated poorly differentiated tumors of 9 different histological subtypes from 69 patients who had received conventional treatments for the presence of CD8+ tumor-infiltrating lymphocytes (TILs), as well as the expression of PD-L1 and microsatellite instability (MSI) markers MLH1, MSH2, MSH6 and PMS2, as biomarkers for immunotherapy. CD8+ TILs were present in 23/69 (33%) cases, PD-L1 expression was observed in 23/69 (33%), and markers for MSI positivity in 5/69 (7%) cases. CD8+ TILs correlated with PD-L1 positivity, while both were mutually exclusive with MSI markers. None of the biomarkers were associated with clinical features as age, gender or tumor stage. Cases with CD8+ TILs and PD-L1 positivity showed a tendency toward worse disease-specific survival. Immune checkpoint inhibitors are emerging as new options for treatment of many tumor types. Our results indicate that also a substantial subset of patients with poorly differentiated sinonasal tumors may be a candidate to be treated with this promising new therapy.
Insights
Poorly differentiated sinonasal tumors have low survival rates. Biomarkers like CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression suggest potential candidates for immunotherapy, offering new treatment hope.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Sinonasal cavities host rare cancers, often poorly differentiated, posing diagnostic and therapeutic challenges.
- Conventional treatments yield low survival rates for these aggressive tumors, highlighting an unmet need for novel therapies.
Purpose of the Study:
- To investigate the prevalence of CD8+ tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and microsatellite instability (MSI) markers in poorly differentiated sinonasal tumors.
- To assess the potential of these biomarkers for predicting immunotherapy response in this patient cohort.
Main Methods:
- Retrospective analysis of 9 histological subtypes from 69 patients with poorly differentiated sinonasal tumors.
- Evaluation of CD8+ TILs, PD-L1 expression, and MSI markers (MLH1, MSH2, MSH6, PMS2) in tumor tissues.
Main Results:
- CD8+ TILs and PD-L1 expression were found in 33% of cases each, correlating with each other but mutually exclusive with MSI positivity (7% of cases).
- No association was observed between these biomarkers and clinical features (age, gender, tumor stage).
- Cases with CD8+ TILs and PD-L1 positivity showed a trend towards worse disease-specific survival.
Conclusions:
- A significant subset of patients with poorly differentiated sinonasal tumors may benefit from immunotherapy targeting immune checkpoints.
- CD8+ TILs and PD-L1 expression serve as potential predictive biomarkers for immunotherapy in sinonasal cancers.
