Several clinical and preclinical mouse model studies, employing PDE-5 inhibitors, such as sildenafil and tadalafil, have demonstrated decreased MDSC accumulation and their immunosuppressive pattern functions by inhibiting iNOS, ARG1, IL4Ra, ROS levels and enabling NK cell anti-tumor cytotoxicity together with activation of anti-tumor response resulting in improved clinical outcome of advanced cancer patients (60, 209–215). Here, NOS2 is linked to neoplasm.