枸杞多糖LBP3通过靶向树突状细胞代谢逆转肿瘤耐抗PD-1单抗治疗的机制
结题报告
批准号:
82004084
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
邓向亮
依托单位:
学科分类:
中西医结合基础理论
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
邓向亮
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中文摘要
最新的研究表明肿瘤微环境使树突状细胞(DCs)代谢改变而影响细胞分化、成熟是肿瘤耐抗PD-1单抗治疗重要原因之一,原位靶向肿瘤组织DCs代谢促进其成熟在协同PD-1单抗治疗黑色素瘤中有增效作用。枸杞多糖可以促进骨髓来源DCs体外成熟和肿瘤组织DCs成熟;本课题前期发现枸杞多糖LBP3具有逆转肿瘤耐抗PD-1单抗治疗的药效,并在体外促进DCs成熟。故提出假说:LBP3可以通过靶向肿瘤组织DCs代谢逆转肿瘤耐抗PD-1单抗治疗。本课题将继续检测LBP3对耐药小鼠肿瘤浸润T细胞、DCs功能的影响;利用DCs体外培养实验结合蛋白组学和代谢组学技术筛选LBP3促进DCs成熟的代谢通路,并在耐药小鼠模型上加以验证;最后采用DCs免疫缺陷小鼠和通路抑制剂干预DCs代谢通路的方法验证LBP3通过靶向DCs代谢通路逆转肿瘤耐抗PD-1单抗治疗的机制。结果为解决肿瘤耐抗PD-1单抗治疗提供中医药策略。
英文摘要
Recent studies have shown that tumor microenvironment changes dendritic cell (DCs) metabolism and affects their differentiation and maturation, which is an important reason for tumor resistance to anti-PD-1 monoclonal antibody therapy. The maturation of dendritic cell can be promoted by targeting metabolism in-situ of tumor tissue, which has synergistic effect with PD-1 mAb in the melanoma tumor. Lycium barbarum polysaccharide can promote maturation of DCs from bone marrow in vitro and tumor tissue in vivo. In the preliminary study of present project, we established a mouse hepatocellular carcinoma transplantation tumor model that was resistant to anti-PD-1 mAb therapy. We found that LBP3 from lycium barbarum polysaccharide with intellectual property rights has reversed tumor resistance to anti-PD-1 mAb therapy and promoted the maturation of DCs in vitro. Thus, we hypothesize that LBP3 reverses tumor resistance to anti-PD-1 mAb therapy by targeting the dendritic cells metabolism in tumor tissues. We will continue to investigate the effects of LBP3 on the function of tumor infiltrating T cells and DCs in the drug-resistant mice. The metabolic pathway that LBP3 promote the maturation of DCs will be screened in vitro experiment using the proteomics and metabolomics techniques, and verified in drug resistant mouse models. Finally, the mechanism of LBP3 reverses tumor resistance to anti-PD-1 mAb therapy by targeting dendritic cell metabolism will be demonstrated by using DCs immunodeficiency mice and pathway inhibitor which targets the metabolic pathway. The results will provide the traditional Chinese medicine therapy strategies for tumor resistance to anti-PD-1 mAb therapy.
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DOI:10.12360/cpb202203078
发表时间:2023
期刊:中国药理学通报
影响因子:--
作者:刘莉;张宝宸;李秀运;吴恩慧;石忠峰;邓向亮
通讯作者:邓向亮
DOI:10.1080/10942912.2022.2057529
发表时间:2022-03
期刊:International Journal of Food Properties
影响因子:2.9
作者:Rongrong Huang;Enhui Wu;Xiangliang Deng
通讯作者:Rongrong Huang;Enhui Wu;Xiangliang Deng
DOI:--
发表时间:2022
期刊:中国生物制品学杂志
影响因子:--
作者:黄凝;祝思宇;李鸿泉;程曦;邓向亮
通讯作者:邓向亮
DOI:--
发表时间:2022
期刊:中医药学报
影响因子:--
作者:程曦;黄凝;李鸿泉;周楷栋;邓向亮
通讯作者:邓向亮
DOI:10.1155/2022/5882136
发表时间:2022
期刊:JOURNAL OF IMMUNOLOGY RESEARCH
影响因子:4.1
作者:Zhang, Baochen;Chen, Kengyu;Liu, Li;Li, Xiuyun;Wu, Enhui;Han, Liang;Shi, Zhongfeng;Deng, Xiangliang
通讯作者:Deng, Xiangliang
基于IRE1α/XBP1通路探讨枸杞多糖LBP3联合PD-1单抗防治肝癌复发和转移的免疫机制
  • 批准号:
    n/a
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2022
  • 负责人:
    邓向亮
  • 依托单位:
枸杞多糖活性片段LBP3通过调节CD8+TILs能量代谢增强小鼠肝癌免疫治疗疗效的机制
  • 批准号:
    --
  • 项目类别:
    省市级项目
  • 资助金额:
    10.0万元
  • 批准年份:
    2019
  • 负责人:
    邓向亮
  • 依托单位:
国内基金
海外基金