A polysaccharide from Dendrobium devonianum induces antitumour immune responses by promoting TLR4-mediated M1 macrophage polarisation

Abstract

Background: DvP-1 is a polysaccharide from D. devonianum which serves as a TLR4 agonist. The present study evaluated the antitumour effects of DvP-1 and investigated the underlying mechanisms.Materials and Methods: CT26 colon carcinoma-bearing mice were intratumorally injected with DvP-1 and tumour size was monitored. The proportion and activity of several kinds of immune cells in the tumour immune microenvironment (TIME) were further examined using a flow cytometer. RAW 264.7 cells were induced to M1 and M2 macrophage polarisation which were used to investigate the effects of DvP-1. TLR4 antagonist as well as several other TLR antagonists were used to validate if DvP-1 act through TLR4.Results: DvP-1 significantly reduced the growth of CT26 colon carcinoma in mice and enhanced antitumour immune responses in the TIME by decreasing the proportion of immunosuppressive Foxp3 + CD4+ Treg cells and increasing the proportion of effector CD4+ T cells, CD8+ T cells, and CD11b+ F4/80+ macrophages. In addition, DvP-1 significantly increased the expression of CD80 and decreased the expression of CD206 on macrophages. Further mechanism study indicated that DvP-1 mainly promoted M1 macrophage polarisation by TLR4.Conclusion: DvP-1 is a promising candidate for enhancing the efficacy of cancer immunotherapy and warrants further development.

Keywords

• Dendrobium devonianum
• polysaccharide
• cancer immunotherapy
• TLR4
• M1 macrophage polarisation