Knockdown of semaphorin 4d (Sema4D) in a human head and neck squamous cell carcinoma (HNSCC) cell line resulted in a loss of MDSC function, as shown by a decrease in the production of the immunosuppressive cytokines arginase-1, TGF-β, and IL-10 by MDSCs. Here, SEMA4D is linked to head and neck squamous cell carcinoma.