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. The distinct tumor microbiome from pancreatic cancer long-term survivors can be used to predict PDAC survival in humans, and transfer of long-term survivor gut microbiomes can alter the tumor microbiome and tumor growth in mouse models.
Original language | English (US) |
---|---|
Pages (from-to) | 795-806.e12 |
Journal | Cell |
Volume | 178 |
Issue number | 4 |
DOIs | |
State | Published - Aug 8 2019 |
Keywords
- CD8
- PDAC
- antibiotics
- cancer survivors
- fecal microbial transplants
- immunoactivation
- microbiota
- pancreatic cancer
- tumor microbiome
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
MD Anderson CCSG core facilities
- Advanced Technology Genomics Core
- Biostatistics Resource Group
- Flow Cytometry and Cellular Imaging Facility
- Microbiome Facility
- Research Animal Support Facility
- Small Animal Imaging Facility
- Tissue Biospecimen and Pathology Resource