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.
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.
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人参多糖改变肠道微生物群和犬尿氨酸/色氨酸比例，增强抗程序性细胞死亡1/程序性细胞死亡配体1（抗PD-1/PD-L1）免疫疗法的抗肿瘤作用。
DOI：
10.1136/gutjnl-2020-321031
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发表时间：
2022-04
期刊：
影响因子：
24.5
通讯作者：
Leung EL
中科院分区：
文献类型：
--
作者：
Huang J;Liu D;Wang Y;Liu L;Li J;Yuan J;Jiang Z;Jiang Z;Hsiao WW;Liu H;Khan I;Xie Y;Wu J;Xie Y;Zhang Y;Fu Y;Liao J;Wang W;Lai H;Shi A;Cai J;Luo L;Li R;Yao X;Fan X;Wu Q;Liu Z;Yan P;Lu J;Yang M;Wang L;Cao Y;Wei H;Leung EL
程序性死亡1及其配体1 （PD-1/PD-L1）免疫疗法是治疗晚期肺癌的一种很有希望的方法，但反应率有待提高。肠道微生物群在免疫治疗致敏中起着至关重要的作用，人参已被证明具有免疫调节潜力。在这项研究中，我们旨在研究人参多糖（GPs）和αPD-1单克隆抗体（mAb）联合处理是否可以通过调节肠道微生物群来增强应答。给同基因小鼠模型注射gp和αPD-1单抗，通过粪便微生物群移植（FMT）和16S PacBio单分子实时测序（SMRT）评估联合治疗对肠道微生物群的致敏抗肿瘤作用。为了评估免疫相关代谢物，对血浆样本进行代谢组学分析。我们发现，GPs通过增加微生物代谢物戊酸和降低l -犬尿氨酸以及Kyn/Trp的比例，增加了αPD-1 mAb的抗肿瘤应答，这有助于抑制调节性T细胞和诱导Teff细胞在联合治疗后。此外，微生物分析显示，临床抗pd -1阻断反应者中异裂副杆菌和普通拟杆菌的丰度高于无反应者。此外，该联合疗法通过将无应答者的肠道菌群重塑为应答者的肠道菌群，使接受FMT的小鼠对PD-1抑制剂的反应变得敏感。我们的研究结果表明，gp联合αPD-1 mAb可能是使非小细胞肺癌患者对抗pd -1免疫治疗敏感的新策略。肠道微生物群可以作为一种新的生物标志物来预测抗pd -1免疫治疗的反应。
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. 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. 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. 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.
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影响因子：
6.4
作者：
Graf J;Ledala N;Caimano MJ;Jackson E;Gratalo D;Fasulo D;Driscoll MD;Coleman S;Matson AP
通讯作者：
Matson AP
影响因子：
10.9
作者：
Laino, Andressa S.;Betts, B. C.;Woods, David M.
通讯作者：
Woods, David M.
影响因子：
32.4
作者：
Britton, Graham J.;Contijoch, Eduardo J.;Faith, Jeremiah J.
通讯作者：
Faith, Jeremiah J.
影响因子：
15.5
作者：
Lagkouvardos, Ilias;Lesker, Till R.;Clavel, Thomas
通讯作者：
Clavel, Thomas
影响因子：
29.4
作者：
Gu, Shoujun;Zaidi, Sobia;Mishra, Lopa
通讯作者：
Mishra, Lopa