Roles of the HGF/Met signaling in head and neck squamous cell carcinoma: Focus on tumor immunity

c-mesenchymal-epithelial transition (Met) is a transmembrane tyrosine kinase receptor of hepatocyte growth factor (HGF). HGF/Met signaling stimulates numerous pathways, including the Ras/mitogenactivated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B and Wnt/beta-catenin pathways, which serve important roles in cell proliferation, survival, motility, invasion and angiogenesis, and promotes the development and progression of tumors. Aberrant HGF/Met signaling is associated with a poor prognosis in several types of tumors, including head and neck squamous cell carcinoma (HNSCC). Although, the HGF/MET pathway and HGF and/or Met inhibitors have been extensively reviewed, their role in tumor immunity remains elusive. The present review article summarizes the findings on the HGF/Met signaling in HNSCC, including gene and protein alterations, biological functions and patient outcomes. Furthermore, the role of HGF/Met in tumor immunity is discussed and the controversial association between the expression of HGF/Met and the prognosis of patients with HNSCC from the perspective of tumor immunity is clarified. Ultimately, the present review proposes a clinical approach that may improve the efficacy of Met therapy for HNSCC, namely the intratumoral administration of Met inhibitors in order to reduce the inhibitory effect on immune cell recruitment. However, further studies are required to provide an improved understanding of the effects of the HGF/Met pathway on the tumor microenvironment, and the effects of HGF and Met inhibitors on immune cells in the tumor environment should be the focus of future studies.