Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment

Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
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DOI:
10.1186/s12967-020-02231-0
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发表时间:
2020-02-03
影响因子:
7.4
通讯作者:
Marchetti, Paolo
Marchetti, Paolo
中科院分区:
医学2区
文献类型:
--
作者:
Botticelli, Andrea;Vernocchi, Pamela;Marchetti, Paolo

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背景:尽管免疫检查点抑制剂(ICI)有效,但只有20-30%的治疗患者表现出长期获益。在肠道微生物群代谢组中发生的代谢变化在本文中被提出作为潜在影响对immunotherapy.Methods的反应的因素:肠道微生物群的代谢组学分析的特征在于在11例受非小细胞肺癌(NSCLC)影响的患者中用抗PD-1 nivolumab二线治疗。通过GC-MS/SPME和H-1-NMR进行代谢组学分析,以检测挥发性和非挥发性代谢物。代谢组学数据进行处理的统计分析和chemometric analysis.Results:四个11例(36%)提出早期进展,而其余的7个11(64%)提出疾病进展后12个月。2-戊酮(酮)和十三烷(烷烃)与早期进展显著相关,相反,短链脂肪酸(SCFA)(即,丙酸,丁酸),赖氨酸和烟酸显着相关的长期有益effics.Conclusions:我们的初步数据表明肠道微生物群代谢途径在影响免疫治疗反应的重要作用。代谢方法可能是一种有前途的策略,有助于通过识别早期进展者和长期应答者患者的微生物群相关“指标”来对癌症患者进行个性化管理。
Background: Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.Methods: The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and H-1-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.Results: Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.Conclusions: Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.