Ganoderma lucidum polysaccharide (GLP) enhances antitumor immune response by regulating differentiation and inhibition of MDSCs via a CARD9-NF-κB-IDO pathway

• Published in: Bioscience reports 2020-06, Vol.40 (6)
• Main Authors: Wang, Yongyong, Fan, Xiaowu, Wu, Xiaowei
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Cancer; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - enzymology; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - pathology; CARD Signaling Adaptor Proteins - metabolism; Cell Differentiation - drug effects; Cell Line, Tumor; Fruiting Bodies, Fungal; Fungal Polysaccharides - isolation & purification; Fungal Polysaccharides - pharmacology; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Male; Mice, Inbred C57BL; Myeloid-Derived Suppressor Cells - drug effects; Myeloid-Derived Suppressor Cells - enzymology; Myeloid-Derived Suppressor Cells - immunology; NF-kappa B - metabolism; Reishi - chemistry; Signal Transduction; Therapeutics & Molecular Medicine; Tumor Burden - drug effects; Tumor Microenvironment
• ISSN: 0144-8463; 1573-4935
• DOI: 10.1042/BSR20201170

A homogeneous polysaccharide (GLP), with an average molecular weight of 4.44 × 104 Da, was isolated and purified from the fruiting bodies of Ganoderma lucidum. In this work, we examined the antitumor activities of GLP using a mouse Lewis lung cancer (LLC) model and explored possible molecular pathways involved in its immunomodulatory mechanism on tumor-host interaction. GLP administration (25 and 100 mg/kg) significantly inhibited tumor growth, as evidenced by the decreased tumor volume and tumor weight, as well as histological features of tumor tissues with concomitant down-regulation of proliferating cell nuclear antigen (PCNA) proliferative marker. Less myeloid-derived suppressor cells (MDSCs) were accumulated in both spleen and tumor tissues from GLP-treated mice. In contrast, the percentage of CD4+ and CD8+ T cells together with the production of Th1-type cytokines (IFN-γ and IL-12) was increased in the spleen of LLC-bearing mice following GLP administration. Furthermore, GLP administration reversed the attenuated expression of CARD9, p-Syk and p-p65, and increased indoleamine 2,3-dioxygenase (IDO) protein expression in MDSCs of LLC-bearing mice. Collectively, our data demonstrated the first time that GLP induced the differentiation of MDSCs and inhibited the accumulation of MDSCs via CARD9-NF-κB-IDO pathway, thus prevented lung cancer development.