Cell · 2019
Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Riquelme Erick, Zhang Yu, Zhang Liangliang, Montiel Maria, Zoltan Michelle, Dong Wenli, Quesada Pompeyo, Sahin Ismet, Chandra Vidhi, San Lucas Anthony, Scheet Paul, Xu Hanwen, Hanash Samir M, Feng Lei, Burks Jared K, Do Kim-Anh, Peterson Christine B, Nejman Deborah, Tzeng Ching-Wei D, Kim Michael P, Sears Cynthia L, Ajami Nadim, Petrosino Joseph, Wood Laura D, Maitra Anirban, Straussman Ravid, Katz Matthew, White James Robert, Jenq Robert, Wargo Jennifer, McAllister Florencia
Аннотация
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.