Structure characterization of a polysaccharide isolated from sugarcane leaves and its macrophage polarization activity and beneficial effects for cisplatin treatment of lung cancer.

Polysaccharides with immunomodulatory functions have drawn increasing attention in cancer immunotherapy. A bioactive polysaccharide, SLP-D2N2, was extracted from the sugarcane (Saccharum sinensis Roxb.) leaves. Structural analysis suggested that the core region of SLP-D2N2 is likely composed primarily of →4)-β-D-xylose-(1→, with a smaller amount of →3,4)-α-D-xylose-(1→. Side chains connect to the O → 3 site of the sugar unit →3,4)-α-D-xylose-(1 → via α-L-arabinofuranose-(1→. SLP-D2N2 significantly promoted macrophage proliferation, enhanced phagocytosis and increased production of TNF-α and IL-6. Flow cytometry indicated that SLP-D2N2 inhibited M2 macrophage polarization while promoting M1 macrophage polarization. When combined with cisplatin, SLP-D2N2 enhanced the drug sensitivity of A549-luc lung cancer cells. SLP-D2N2 was found to stimulate the TLR4 signaling pathway to induce macrophage polarization toward the M1 type, thereby facilitating synergistic anti-tumor effects. In a lung cancer mouse model established with A549-luc cells, SLP-D2N2 increased M1 macrophage polarization and augmented immune activity. When administered alongside cisplatin, SLP-D2N2 exhibited substantial synergistic anti-tumor effects while reducing the cardiotoxicity and nephrotoxicity typically associated with cisplatin treatment. These findings advance the expanding field of research on bioactive polysaccharides and their roles in cancer immunotherapy.