Lepidium meyenii Walpers polysaccharide and its cationic derivative re-educate tumor-associated macrophages for synergistic tumor immunotherapy. (15th December 2020)

• Record Type: Journal Article
• Authors: Guo, Tingting; Yang, Ye; Gao, Mingju; Qu, Yuan; Guo, Xiaoxi; Liu, Yuan; Cui, Xiuming; Wang, Chengxiao
• Is Part Of: Carbohydrate polymers. Volume 250(2020)
• Publication Date: 2020-12-15
• Subjects: Polysaccharides -- Lepidium meyenii Walp. -- Cationization -- Tumor-associated macrophages -- Immunotherapy; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2020.116904
• Languages: English
• ISSNs: 0144-8617

Abstract

Highlights: A polysaccharide (MPW) was isolated from Lepidium meyenii Walp. (Maca). MPW is mainly composed of →4) -α-D-Glcp- (1 → glycoside bond. MPW showed significant in vivo tumor immunotherapy activity. MPW and its cationic derivative (C-MPW) can re-direct TAMs to M1 phenotype. C-MPW exhibited a stronger tumor immunotherapy activity than MPW. Abstract: In the current study, we developed a synergistic chemo-immunotherapy using doxorubicin (Dox) and a natural polysaccharide as immunomodulator. First, we isolated a polysaccharide (MPW) from the root of Lepidium meyenii Walp. (maca) and characterized its chemical properties. MPW contains → 4) -α-D-Glcp- (1 → glycosidic bonds, while the terminal α-D-Glcp- (1 → group is connected to the main chain through an O -6 bond. This polysaccharide was then modified by cationization (C-MPW) to enhance immunoregulatory activity. MPW and C-MPW were combined with Dox and their chemo-immunotherapy effects on 4T1 tumor-bearing mice were assessed. Results indicated that the combination of MPW/C-MPW exerted a stronger anti-tumor effect than Dox alone, while reducing systemic toxicity and inhibiting tumor metastasis. In addition, MPW and C-MPW exerted tumor immunotherapy effects through the NF-κB, STAT1, and STAT3 signaling pathways, redirecting TAMs to the M1 phenotype that facilitates immunological responses against tumors. As a result, the immunosuppressive tumor microenvironment was remodeled into an immune-activated state due to enhanced secretion of IL-12, TNF-α, and INF-γ. Moreover, C-MPW exerted a stronger immunomodulatory effect than MPW. In conclusion, MPW and its cationic derivative are promising tools for cancer immunotherapy.