Format

Send to

Choose Destination
Cell. 2019 Aug 8;178(4):795-806.e12. doi: 10.1016/j.cell.2019.07.008.

Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes.

Author information

1
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Center for Integrative Biology, Faculty of Science, Universidad Mayor, Santiago, Chile.
2
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
5
Department of Engineering, Texas Southern University, Houston, TX, USA.
6
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
7
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
8
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
9
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
10
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
11
Departments of Medicine, Oncology and Molecular Microbiology & Immunology, Johns Hopkins University School of Medicine and the Bloomberg School of Public Health, Baltimore, MD, USA.
12
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
13
Department of Pathology and The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
14
Sheikh Ahmed Pancreatic Cancer Research Center, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
15
Resphera Biosciences, Baltimore, MD, USA.
16
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
17
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
18
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: fmcallister@mdanderson.org.

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.

KEYWORDS:

CD8; PDAC; antibiotics; cancer survivors; fecal microbial transplants; immunoactivation; microbiota; pancreatic cancer; tumor microbiome

PMID:
31398337
DOI:
10.1016/j.cell.2019.07.008

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center