期刊
GUT
卷 71, 期 4, 页码 734-745出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/gutjnl-2020-321031
关键词
cancer; drug resistance; prebiotic; probiotics; cancer immunobiology
资金
- Macao Science and Technology Development Fund [0096/2018/A3, 001/2020/ALC]
- NSFC overseas and Hong Kong and Macao Scholars Cooperative Research Fund Project [81828013]
This study demonstrated that the combination of GPs and alpha PD-1 mAb enhanced the antitumor response by modulating gut microbiota. The GPs increased microbial metabolites and reshaped gut microbiota towards responders, sensitizing non-small cell lung cancer patients to anti-PD-1 immunotherapy. Additionally, gut microbiota could serve as a novel biomarker to predict the response to anti-PD-1 immunotherapy.
Objective Programmed death 1 and its ligand 1 (PD-1/PD-L1) immunotherapy is promising for late-stage lung cancer treatment, however, the response rate needs to be improved. Gut microbiota plays a crucial role in immunotherapy sensitisation and Panax ginseng has been shown to possess immunomodulatory potential. In this study, we aimed to investigate whether the combination treatment of ginseng polysaccharides (GPs) and alpha PD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota. Design Syngeneic mouse models were administered GPs and alpha PD-1 mAb, the sensitising antitumour effects of the combination therapy on gut microbiota were assessed by faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing. To assess the immune-related metabolites, metabolomics analysis of the plasma samples was performed. Results We found GPs increased the antitumour response to alpha PD-1 mAb by increasing the microbial metabolites valeric acid and decreasing L-kynurenine, as well as the ratio of Kyn/Trp, which contributed to the suppression of regulatory T cells and induction of T-eff cells after combination treatment. Besides, the microbial analysis indicated that the abundance of Parabacteroides distasonis and Bacteroides vulgatus was higher in responders to anti-PD-1 blockade than non-responders in the clinic. Furthermore, the combination therapy sensitised the response to PD-1 inhibitor in the mice receiving microbes by FMT from six non-responders by reshaping the gut microbiota from non-responders towards that of responders. Conclusion Our results demonstrate that GPs combined with alpha PD-1 mAb may be a new strategy to sensitise non-small cell lung cancer patients to anti-PD-1 immunotherapy. The gut microbiota can be used as a novel biomarker to predict the response to anti-PD-1 immunotherapy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据