Abstract. Background: The cellular composition of the tumor microenvironment (TME) at the invading front of oral squamous cell carcinomas (OSCCsThe growth of oral squamous cell carcinoma cells is influenced by its stroma. Stromal cells such as mast cells (MCs), cancer-associated fibroblasts (CAFs), tumorassociated macrophages (TAMs), endothelial cells, pericytes, smooth muscle cells and lymphocytes promote tumor growth, local infiltration, proliferation, neovascularization and escape from immune defense (1). Such cancer-amended stroma is referred to as the tumor microenvironment (TME) (2), and is probably as important as the cancer itself in facilitating cancer cell invasion and metastasis. In the current study of early-stage oral squamous cell carcinomas (OSCCs), we examined the significance of MCs, CAFs, TAMs and endothelial cells in the TME of the invasive front, and their influence on disease recurrence. The MC findings were further explored in a larger cohort of patients with head and neck squamous cell carcinoma.MCs are especially present in surface mucosa such as the skin, bronchial tract, lungs and digestive tract, conjunctiva, nose and mouth, and are best known for their role in allergic immune reactions (3). The TME in OSCC contains more MCs than normal oral mucosa (4), but their role in TME is intricate and poorly understood. These MCs may promote cancer growth by stimulating angiogenesis and tissue remodeling, but also exert anticancerous effects, depending on cofactors and cell location (5).CAFs represent a common functional state of cancerstimulated mesenchymal cells. Their cell of origin is 5499

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High nuclear SOX2 expression in the invasive front was associated with dramatic longer disease-free period than low SOX2-expressing carcinomas after post-operative radiotherapy in small OSCCs. The result suggested that high nuclear SOX2 expression at the invasive front may predict radiosensitivity.