In this study, we systematically elucidated the expression and activation characteristics, as well as the functional roles, of the classical Smad2/3 signaling pathway and the non-classical PI3K/AKT signaling pathway in the context of tumor MO-MDSC differentiation blockade and expansion, suggesting that the influence of Tgfβ1 on the maturation and expansion of MO-MDSC is not uniform but variable and subject to regulation. The gene discussed is SMAD2; the disease is neoplasm.