| Literature DB >> 31398337 |
Erick Riquelme1, Yu Zhang2, Liangliang Zhang3, Maria Montiel2, Michelle Zoltan2, Wenli Dong4, Pompeyo Quesada2, Ismet Sahin5, Vidhi Chandra2, Anthony San Lucas6, Paul Scheet6, Hanwen Xu2, Samir M Hanash7, Lei Feng4, Jared K Burks8, Kim-Anh Do4, Christine B Peterson4, Deborah Nejman9, Ching-Wei D Tzeng10, Michael P Kim10, Cynthia L Sears11, Nadim Ajami12, Joseph Petrosino12, Laura D Wood13, Anirban Maitra14, Ravid Straussman9, Matthew Katz10, James Robert White15, Robert Jenq16, Jennifer Wargo17, Florencia McAllister18.
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 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. Published by Elsevier Inc.Entities:
Keywords: CD8; PDAC; antibiotics; cancer survivors; fecal microbial transplants; immunoactivation; microbiota; pancreatic cancer; tumor microbiome
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Year: 2019 PMID： 31398337 PMCID： PMC7288240 DOI： 10.1016/j.cell.2019.07.008
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582