Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes
Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes
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DOI：
10.1016/j.cell.2019.07.008
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发表时间：
2019-08-08
期刊：
影响因子：
64.5
通讯作者：
McAllister, Florencia
中科院分区：
文献类型：
--
作者：
Riquelme, Erick;Zhang, Yu;McAllister, Florencia
大多数被诊断为切除胰腺癌（PDAC）的患者生存期不到5年，但一小部分患者生存期更长。在此，我们将分析肿瘤微生物群和免疫系统在影响长期生存中的作用。我们采用16 S rRNA基因测序分析了短期生存（STS）和长期生存（LTS）的PDAC患者的肿瘤微生物组组成。我们发现LTS患者肿瘤微生物组中有较高的α-多样性，并鉴定了一种肿瘤内微生物组特征（假黄单胞菌-链霉菌-糖多孢菌-克劳氏芽孢杆菌），在发现和验证队列中均能高度预测长期生存率。通过STS、LTS或对照供体的人-小鼠粪便微生物群移植（FMT）实验，我们能够不同地调节肿瘤微生物群并影响肿瘤生长和肿瘤免疫浸润。我们的研究表明，PDAC微生物组的组成，这是交叉交谈的肠道微生物组，影响宿主的免疫反应和疾病的自然史。
Most patients diagnosed with resected pancreatic adenocarcinoma (PDAC) survive less than 5 years, but a minor subset survives longer. Here, we dissect the role of the tumor microbiota and the immune system in influencing long-term survival. Using 16S rRNA gene sequencing, we analyzed the tumor microbiome composition in PDAC patients with short-term survival (STS) and long-term survival (LTS). We found higher alpha-diversity in the tumor microbiome of LTS patients and identified an intra-tumoral microbiome signature (Pseudoxanthomonas-Streptomyces-Saccharopolyspora-Bacillus clausii) highly predictive of long-term survivorship in both discovery and validation cohorts. Through human-into-mice fecal microbiota transplantation (FMT) experiments from STS, LTS, or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration. Our study demonstrates that PDAC microbiome composition, which cross-talks to the gut microbiome, influences the host immune response and natural history of the disease.