089 | Epithelial-immune cell crosstalk in salivary gland tumors: implications for tumor progression and diagnostic assessment

Martina Sausa¹, Giuseppe Vergilio¹, Rosario Barone¹, Rossana Porcasi², Prince Ofori³, Fatima Azhraa Haddad^3|4, Francesca Rappa^1|5, Francesca Levi-Schaffer,³ Angelo Leone^1|3 | ¹Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Italy; ²Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Italy; ³Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel; ⁴Department of Otolaryngology Head and Neck Surgery, Hadassah Medical Center, Hebrew University of Jerusalem, Israel; ⁵Institute of Translational Pharmacology, National Research Council of Italy CNR, Palermo, Italy.

Salivary gland tumors (SGTs) comprise a heterogeneous group of epithelial neoplasms with marked histological and biological variability. While most SGTs are benign, malignant forms such as squamous cell carcinoma (SCC) exhibit aggressive behavior, characterized by local invasiveness, early metastasis, and poor response to conventional therapies. A central mechanism in tumor progression is epithelial–mesenchymal transition (EMT), in which epithelial cells lose polarity and intercellular adhesion, acquiring migratory and apoptosis-resistant properties; loss of E-cadherin and increased vimentin expression are key hallmarks of this process. The salivary gland tumor microenvironment plays a critical role in EMT regulation, although the underlying molecular mechanisms remain largely unclear. Among immune components, mast cells have emerged as important modulators through the release of pro-tumorigenic mediators, including mast cell tryptase (MCT), which promotes angiogenesis, extracellular matrix remodeling, and invasive signaling in epithelial cells. In parallel, the inhibitory receptor CD300a, expressed on immune cells and aberrantly on tumor epithelial cells, appears to regulate mast cell degranulation and immune homeostasis within the tumor microenvironment. This study evaluates the histological and immunohistochemical expression of MCT and CD300a in healthy salivary tissues, pleomorphic adenoma, and SCC, focusing on their interplay in EMT regulation and tumor progression. Our findings indicate that mast cell infiltration and MCT release correlate with E-cadherin loss and a more invasive phenotype, while CD300a shows a context-dependent role, exerting predominantly inhibitory effects in benign lesions and pro-tumorigenic functions in malignant tumors. Co-expression of MCT and CD300a in ductal cells may represent a marker of aggressiveness and metastatic potential. Overall, the integrated analysis of MCT and CD300a provides new insights into immune–epithelial interactions in salivary gland tumors and may support the development of therapeutic strategies targeting the tumor microenvironment to counteract EMT and restore tissue homeostasis.