SMAD4 and neoplasm: It was shown that TGF-β acting through SMAD4 and SMAD7 transduction enhances the recruitment of monocytes and activation of macrophages, suppresses the functioning of anti-tumor T-cells and generates immunosuppressive TIME facilitating immune evasion mechanisms and tumor progression (Derynck et al., 2021; Ivanova et al., 2018).