Effects of polysaccharides from the rhizome of Menispermum dauricum DC on alleviating chemotherapy-induced immune damage and the immunosuppressive tumor microenvironment associated with PD-1/PD-L1 regulation.

In this study, we established a metastatic tumor model by tail vein injection of fluorescent-labeled Lewis lung cancer cells. We systematically evaluated the in vivo antitumor effects of the rhizome of Menispermum dauricum polysaccharides (MDP), a homogeneous polysaccharide obtained through sequential chromatographic purification, its efficacy in alleviating cyclophosphamide (CTX)-induced chemotherapy damage, and its ability to improve the immunosuppressive tumor microenvironment (TME). We also investigated whether its mechanism is associated with the PD-1/PD-L1 pathway. Concurrently, an in vitro tumor-associated macrophage (TAM) model was established to validate the regulatory effects of MDP on macrophage polarization. The results indicated that MDP effectively inhibits tumor growth and prevents metastasis in the metastatic tumor model. Combined with CTX, MDP alleviated CTX-induced weight loss and damage to the spleen and thymus while exhibiting synergistic antitumor effects by reducing the lung index and increasing the lung index suppression rate. In terms of immune regulation, MDP promotes Th1 differentiation, suppresses Th2 differentiation, reduces the proportion of Treg cells, and activates Th17 and CD8+ cytotoxic T cells, thereby improving the TME. It also promotes TAM polarization toward the M1 phenotype while inhibiting M2 polarization, significantly elevating the levels of M1 macrophage activators (LPS and IFN-γ) while decreasing those of M2 macrophage immunosuppressive factors (TGF-β and IL-10). This effect may be associated with the downregulation of PD-1/PD-L1 protein expression. In vitro experiments further validated the ability of MDP to induce TAMs to reverse from the M2 to the M1 phenotype. In summary, MDP shows significant immunomodulatory and antitumor potential, supporting its development as a polysaccharide drug for tumor treatment or adjuvant therapy.