@article{1aafcf9a60de4ad08c481d141ada52c0,
title = "Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes",
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.",
author = "Erick Riquelme and Yu Zhang and Liangliang Zhang and Maria Montiel and Michelle Zoltan and Wenli Dong and Pompeyo Quesada and Ismet Sahin and Vidhi Chandra and {San Lucas}, Anthony and Paul Scheet and Hanwen Xu and Hanash, {Samir M.} and Lei Feng and Burks, {Jared K.} and Kim-Anh Do and Peterson, {Christine B.} and Deborah Nejman and Tzeng, {Ching-Wei D.} and Kim, {Michael P.} and Sears, {Cynthia L.} and Nadim Ajami and Joseph Petrosino and Wood, {Laura D.} and Anirban Maitra and Ravid Straussman and Matthew Katz and White, {James Robert} and Robert Jenq and Jennifer Wargo and Florencia McAllister",
note = "We thank Peter Davies for his scientific vision and feedback during the study conduction. F.M. has been funded by the American Gastroenterological Association Research Foundation, a PanCAN/AACR Career Development Award (14-20-25-MCAL), Emerson Collective Award, and K12 Paul Calabresi Clinical Scholarship Award (K12CA088084-16A1). A.M. and F.M. were funded by MD Anderson Philanthropic Funds and Stand Up To Cancer-Lustgarten Foundation Pancreatic Cancer Interception Translational Cancer (SU2C-AACR-DT25-17) administered by the American Association for Cancer Research. E.R. acknowledges Becas Chile. P.Q. was supported by the National Cancer Institute (R25E CA056452) and a MD Anderson{\textquoteright}s Cancer Center support grant (CA016672). Author Contributions Conceptualization, E.R., Y.Z., and F.M.; Methodology, L.Z., J.R.W., J.K.B., and N.A.; Investigation, E.R., Y.Z., L.Z., J.R.W., M.Z., W.D., L.F., P.Q., I.S., V.C., P.S., H.X., and D.N.; Resources, M.M., M.P.K., L.D.W., A.M., and M.K.; Supervision, S.M.H., J.P., K.-A.D., C.B.P., R.S., R.J., J.W., and F.M.; Funding acquisition, A.M. and F.M.; Writing – Original Draft, E.R. and F.M.; Writing – Review & Editing, E.R., Y.Z., L.Z., J.R.W., A.M., R.J., C.L.S., and F.M. Declaration of Interests J.W. is an inventor on a US patent application (PCT/US17/53.717) submitted by the UT MDACC and reports compensation for speaker{\textquoteright}s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune, and Bristol-Myers Squibb (BMS). J.W. serves as a consultant and advisory board member for Roche and Genentech, Novartis, AstraZeneca, GlaxoSmithKline (GSK), BMS, Merck, Biothera Pharmaceuticals, and Microbiome DX and receives research support from GSK, Roche/Genentech, BMS, and Novartis. A.M. and S.M.H. receive royalties from Hangzhou Guangkeande (Cosmos) Biotechnology Company LTD for a license managed by the MD Anderson Conflict of Interest Committee. F.M., E.R., and Y.Z. are filing a patent with findings presented in this manuscript.",
year = "2019",
month = aug,
day = "8",
doi = "https://doi.org/10.1016/j.cell.2019.07.008",
language = "الإنجليزيّة",
volume = "178",
pages = "795--806, e1--e12",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "4",
}