The dense fibrotic peri-tumoral stroma observed in the current work, demonstrating collagen I and III, with Sema4D+ve/high HNSCC tumor cells, in addition to the role for Sema4D in induction of collagen deposition by fibroblasts (Figure 3A–3G) (Figure 6), reveals another prospective by which Sema4D induces immune suppression. The gene discussed is SEMA4D; the disease is head and neck squamous cell carcinoma.