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Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer

作者:Wenshuai Li, Qi Zhou, Bin Lü, Na Li, Xiqing Bian, Lirong Chen, Mingjia Kong, Yuru Shen, Wanwei Zheng, Jun Zhang, Feifei Luo, Zhongguang Luo, Jie Liu, Jian‐Lin Wu · 发表于:Journal of Agricultural and Food Chemistry · 年份:2024 · DOI:10.1021/acs.jafc.3c08385 · 被引用次数:66 · 研究领域:Fungal Biology and Applications、Pharmacological Effects of Natural Compounds、Phytochemistry and Bioactivity Studies

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8 + T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.