Sema4D is over expressed in HNSCC, prostate, colon, breast, lung, cervical and ovarian malignancies [22–25] and it was described to induce tumor angiogenesis through binding to its high affinity receptor Plexin-B1 on endothelial cells promoting their proliferation and organization [24]. The gene discussed is SEMA4D; the disease is head and neck squamous cell carcinoma.