Tadalafil, a PDE-5 inhibitor decreases circulating MDSCs, lowers iNOS and arginase expression in these cells, and enriches tumor-specific T cells in HNSCC patients (91) and it is being clinically tested in patients with multiple myeloma in combination with lenalidomide (NCT01858558) and in patients with HNSCC in combination with mucin 1 vaccine (NCT02544880). Here, NOS2 is linked to head and neck squamous cell carcinoma.