HNSCC with Sema4D-positive tumor cells correlated with dense noninflamed peritumoral stroma (6), and in vitro models showed that HNSCC produced sSema4D can upregulate myeloid-derived suppressor cells (MDSC) (24–26) and plays a role in extracellular matrix (ECM) deposition by fibroblasts (11). The gene discussed is SEMA4D; the disease is neoplasm.