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Program Number: B044
Session Name: Poster Session

High hybrid epithelial-mesenchymal states are associated with unique tumor microenvironment and worse overall survival in head and neck cancer patients

Daniel A Ruiz-Torres, MD¹; Anuraag S Parikh, MD²; Sara Cavallaro, PhD¹; Joao P Oliveira-Costa, DMD, PhD¹; Jeremy D Richmon, MD³; Kevin S Emerick, MD³; Daniel G Deschler, MD³; Mark A Varvares, MD³; Derrick T Lin, MD³; William C Faquin, MD, PhD⁴; Bradley E Bernstein, MD, PhD⁵; Sidharth V Puram, MD, PhD⁶; Shannon L Stott, PhD¹; ¹Massachusetts General Hospital Cancer Center; ²Columbia University Department of Otolaryngology-Head and Neck Surgery; ³Department of Otolaryngology, Massachusetts Eye and Ear; ⁴Department of Pathology, Massachusetts General Hospital; ⁵Broad Institute of Harvard and MIT; ⁶Department of Otolaryngology, Washington University School of Medicine

Background: Metastasis is a major cause of morbidity and mortality in head and neck squamous cell carcinoma (HNSCC). At diagnosis, distant metastases of head and neck cancers are present in about 10% of cases, with an additional 20-30% developing metastases during their disease. However, the mechanisms that trigger metastasis remain poorly understood. The presence of a hybrid epithelial-mesenchymal state (hEM) among malignant cells could explain their metastatic capabilities. However, the spatial distribution of hEM cells in the tumor microenvironment (TME) remains understudied.

Methods: In this retrospective cohort study, we applied a multi-plex immunohistochemistry (mIF) protocol on tissue microarrays from 63 patients with newly diagnosed HPV- HNSCC treated with surgery, followed by risk-adjusted post-operative treatment at Massachusetts Eye and Ear. The staining panels included a hEM panel (p63, LAMC2, VIM, LAMB3, PDPN, SPRR1B) and an immune panel (CD8, CD4, CD20, CD163, PD-1, panCK). The spatial distribution of each marker in tumor and stroma compartments was calculated.  Patients were split into high or low hEM based on the median percentage of LAMC2+LAMB3+ cells for the cohort.

Results: The median follow-up was 23 months (range 1-106). Most patients had tongue 27/63 (41%), followed by alveolar ridge 15/63 (23%) SCC. 45/63 (65%) received adjuvant chemoradiotherapy, and 27/63 (42%) experienced recurrence. Patients with a higher percentage of hEMT (based on LAMC2+LAMB3+) displayed statistically significant lower densities of CD4+PD1+ (Wilcoxon test p=0.004) and CD20+ cells (Wilcoxon test p=0.0003). Importantly, these patients also had worse 5-year overall survival (HR=2.83; 95% CI: 1.01-7.96).

Conclusion: High hEM malignant cells in the TME of HNSCC patients were associated with a distinct organization of immune cells and worse overall survival. Future studies should explore the complex interplay between these malignant and immune subpopulations as well as the role of hEM as a biomarker in HNSCC.

 

 

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