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小擎子
(2022-01-26 17:07):
#paper doi:10.1016/j.cell.2019.07.008 Cell, 2019, Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes。研究肿瘤微生物的一篇经典论文。测试了胰腺癌的肿瘤微生物,收集了两组来源数据,每组数据都包含长期存活患者(LTS,中位生存期10.1年)和短期存活患者(STS,中位生存期1.6年)。测试了组织微生物和肠道微生物,文献中也收集了正常人的胰腺组织微生物和肠道微生物。发现LTS和STS的微生物组成模式不同,同时富集在LTS和STS里的微生物种类不同。又额外使用FMT的方法,在小鼠身上做了实验,实验设计较为严谨,小鼠移植肿瘤前使用抗生素及FMT处理。小鼠实验发现,来源于LTS的FMT的小鼠的肿瘤大小明显缩小,STS的FMT的肿瘤最大,正常人的FMT居中。为了验证是微生物的影响,在移植FMT后也做了抗生素处理做对照。实验发现,FMT(粪便微生物群移植)可以改变小鼠的肠道微生物,同时小鼠肿瘤里的微生物也会随之变化。LTS的微生物组成情况与正常人不同,来自LTS的微生物移植对小鼠的肿瘤有消融效果。
Abstract:
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 …
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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.
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