Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.
Adult
Aged
Animals
Bacteria
/ classification
Carcinoma, Pancreatic Ductal
/ microbiology
Cell Line, Tumor
Cohort Studies
Fecal Microbiota Transplantation
Feces
/ microbiology
Female
Gastrointestinal Microbiome
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Pancreatic Neoplasms
/ microbiology
RNA, Ribosomal, 16S
/ genetics
Sequence Analysis, RNA
Survival Rate
CD8
PDAC
antibiotics
cancer survivors
fecal microbial transplants
immunoactivation
microbiota
pancreatic cancer
tumor microbiome
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
08 08 2019
08 08 2019
Historique:
received:
15
07
2018
revised:
06
03
2019
accepted:
08
07
2019
entrez:
10
8
2019
pubmed:
10
8
2019
medline:
10
5
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31398337
pii: S0092-8674(19)30773-1
doi: 10.1016/j.cell.2019.07.008
pmc: PMC7288240
mid: NIHMS1537195
pii:
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
795-806.e12Subventions
Organisme : NCI NIH HHS
ID : K08 CA218690
Pays : United States
Organisme : NCI NIH HHS
ID : K12 CA088084
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA056452
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Published by Elsevier Inc.
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