SMAD3 and neoplasm: However, Smad3 expression was significantly downregulated in CD11b+Gr-1+ tumor MDSC, which exhibited immunosuppressive functions and elevated levels of immunosuppressive molecules such as arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and reactive oxygen species (ROS), compared to wild-type cells (Fig. 1A and Supplementary Fig. 1A–C).