Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes

Authors

E. Riquelme, University of Texas MD Anderson Cancer Center
Yu Zhang, University of Texas MD Anderson Cancer Center
Liangliang Zhang, University of Texas MD Anderson Cancer Center
M. Montiel, University of Texas MD Anderson Cancer Center
Michelle Zoltan, University of Texas MD Anderson Cancer Center
W. Dong, University of Texas MD Anderson Cancer Center
Pompeyo Quesada, University of Texas MD Anderson Cancer Center
I. Sahin, Texas Southern University
V. Chandra, University of Texas MD Anderson Cancer Center
Anthony San Lucas, University of Texas MD Anderson Cancer Center
Paul Scheet, University of Texas MD Anderson Cancer Center
Hanwen Xu, University of Texas MD Anderson Cancer Center
Samir M. Hanash, University of Texas MD Anderson Cancer Center
Lei Feng, University of Texas MD Anderson Cancer Center
Jared K. Burks, University of Texas MD Anderson Cancer Center
Kim Anh Do, University of Texas MD Anderson Cancer Center
Christine B. Peterson, University of Texas MD Anderson Cancer Center
Deborah Nejman, Weizmann Institute of Science Israel
Ching Wei D. Tzeng, University of Texas MD Anderson Cancer Center
Michael P. Kim, University of Texas MD Anderson Cancer Center
Cynthia L. Sears, Johns Hopkins School of Medicine

Document Type

Article

Publication Date

8-8-2019

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.

Recommended Citation

Riquelme, E.; Zhang, Yu; Zhang, Liangliang; Montiel, M.; Zoltan, Michelle; Dong, W.; Quesada, Pompeyo; Sahin, I.; Chandra, V.; 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.; and Sears, Cynthia L., "Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes" (2019). Faculty Publications. 105.
https://digitalscholarship.tsu.edu/facpubs/105