Abstract 3672: Semaphorin 4D in human head & neck cancer: A promising predictive biomarker for the peri-tumoral stromal phenotype

Abstract

Abstract Semaphorin 4D in human head and neck cancer: A promising predictive biomarker for the peri-tumoral stromal phenotype The search for biomarkers that can predict the tumor stromal phenotype in cancer patients is a challenge in the field. Semaphorin 4D (Sema4D), known for its various effects in the nervous, vascular and immune system, plays an important role in regulating pro and anti-inflammatory responses. It is over-expressed in Head and Neck cancer (HNC) as well as in other epithelial malignancies. We have recently described that HNC-associated Sema4D modulates the inflammatory profile to an immune-suppressive phenotype by inducing the expansion of myeloid derived suppressor cells. The purpose of this study was to determine the prognostic value of Sema4D as a biomarker for immune suppression in human HNC tissue and sera. Immunohistochemistry showed Sema4D+ve/high tumors to correlate positively with Stage III disease (p=0.014), and nodal metastasis (p=0.117). Sema4D+ve/high tumors correlated directly with dense fibrotic peri-tumoral stroma (p=0.0001) and inversely with tumor-associated inflammatory cells (TAIs) (p=0.0006). Knockdown of Sema4D in HNC cell lines resulted in significant reduction of TGF-β1 production (p=0.0016). Sema4D+ve/high tumor cells inversely correlated with the programmed death ligand 1 (PDL-1) positive tumors. Finally, Sema4D was detected in sera of HNC patients at higher levels compared to healthy donors (p <0.0001). In conclusion, we present a novel Sema4D+ve/high HNC tumor phenotype; with dense fibrotic peri-tumoral stroma. We also present Sema4D as a diagnostic biomarker in sera of HNC patients that can also be a promising predictor of the tumor stromal phenotype. This is of clinical interest as a predictive biomarker and a promising target for co-inhibition to sensitize patients for standard immunotherapy. [1-4]