Anti-tumor effect of Crocus sativus petals polysaccharides by reconstructing tumor microenvironment

Two polysaccharides from Crocus sativus petals (PCSPs), PCSPA and PCSPB have been previously reported to possess the immunopotentiation activity and improve innate immunity in mice. In this study, PCSPB was evaluated for the anti-tumor activity and explored its immunological mechanisms based on tumor microenvironment (TME) using S180 sarcoma-bearing mice. Although PCSPB showed the lower toxicity to a series of tumor cells, it significantly and dose-dependently suppressed the growth of S180 sarcomas transplanted in mice. HE staining, immunohistochemical analysis, and TUNEL assay revealed that PCSPB significantly induced tumor cell necrosis, apoptosis, and vessel disruption in sarcoma tissues. Meanwhile, PCSPB markedly decreased the levels of inflammatory factors TGF-β, IFN-γ, IL-10 and TNF-α and down-regulated the mRNA expression levels of TGF-β and TNF-α in tumor tissues. Flow cytometric analysis showed that PCSPB significantly increased the proportion of CD8⁺ T cells and NK cells, but decreased that of regulatory T cells (Tregs), total myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) in sarcoma tissues. Furthermore, immunofluorescence assay demonstrated that PCSPB noteworthily reprogrammed TAMs from a tumorigenic M2 towards an antitumorigenic M1 phenotype in S180 tissues. These findings demonstrated that PCSPB might exert the anti-tumor activity by reconstructing TME and could act as an anti-tumor candidate with low toxicity.