RT Journal Article
SR Electronic
T1 Ginseng polysaccharides alter the gut microbiota and kynurenine/tryptophan ratio, potentiating the antitumour effect of antiprogrammed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) immunotherapy
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP gutjnl-2020-321031
DO 10.1136/gutjnl-2020-321031
A1 Jumin Huang
A1 Di Liu
A1 Yuwei Wang
A1 Liang Liu
A1 Jian Li
A1 Jing Yuan
A1 Zhihong Jiang
A1 Zebo Jiang
A1 WL Wendy Hsiao
A1 Haizhou Liu
A1 Imran Khan
A1 Ying Xie
A1 Jianlin Wu
A1 Yajia Xie
A1 Yizhong Zhang
A1 Yu Fu
A1 Junyi Liao
A1 Wenjun Wang
A1 Huanling Lai
A1 Axi Shi
A1 Jun Cai
A1 Lianxiang Luo
A1 Runze Li
A1 Xiaojun Yao
A1 Xingxing Fan
A1 Qibiao Wu
A1 Zhongqiu Liu
A1 Peiyu Yan
A1 Jingguang Lu
A1 Mingrong Yang
A1 Lin Wang
A1 Yabing Cao
A1 Hong Wei
A1 Elaine Lai-Han Leung
YR 2021
UL http://gut.bmj.com/content/early/2021/05/18/gutjnl-2020-321031.abstract
AB 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 αPD-1 monoclonal antibody (mAb) could sensitise the response by modulating gut microbiota.Design Syngeneic mouse models were administered GPs and αPD-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 αPD-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 Teff 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 αPD-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.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information.