Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes

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 micro...

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Bibliographic Details
Published in:Cell Vol. 178; no. 4; p. 795
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 08.08.2019
Subjects:
Adult
Aged
Animals
Bacteria - classification
Carcinoma, Pancreatic Ductal - microbiology
Carcinoma, Pancreatic Ductal - mortality
Cell Line, Tumor
Cohort Studies
Fecal Microbiota Transplantation
Feces - microbiology
Female
Gastrointestinal Microbiome
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Pancreatic Neoplasms - microbiology
Pancreatic Neoplasms - mortality
RNA, Ribosomal, 16S - genetics
Sequence Analysis, RNA
Survival Rate
microbiota
pancreatic cancer
PDAC
cancer survivors
fecal microbial transplants
CD8
immunoactivation
antibiotics
tumor microbiome
ISSN:1097-4172, 1097-4172
Online Access:Get more information
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Summary: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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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2019.07.008