Food Science and Technology Department

 

Authors

Yan Li, Sanford Burnham Prebys Medical Discovery Institute
Roberto Tinoco, Sanford Burnham Prebys Medical Discovery Institute & University of California
Lisa Elmén, Sanford Burnham Prebys Medical Discovery Institute
Igor Segota, Sanford Burnham Prebys Medical Discovery Institute
Yibo Xian, University of Nebraska- Lincoln
Yu Fujita, Sanford Burnham Prebys Medical Discovery Institute
Avinash Sahu, University of Maryland
Raphy Zarecki, Tel Aviv University
Kerrie Marie, National Institutes of Health
Yongmei Feng, Sanford Burnham Prebys Medical Discovery Institute
Ali Khateb, Technion Israel Institute of technology
Dennie T. Frederick, Harvard Medical School
Shiri K. Ashkenazi, Technion Israel Institute of technology
Hyungsoo Kim, Sanford Burnham Prebys Medical Discovery Institute
Eva Guijarro Perez, National Institutes of Health
Chi-Ping Day, National Institutes of Health
Rafael S. Segura Muñoz, University of Nebraska- Lincoln
Robert Schmaltz, University of Nebraska- Lincoln
Shibu Yooseph, University of Central Florida
Miguel A. Tam, BioLegend
Tongwu Zhang, National Cancer Institute
Emily Avitan-Hersh, Technion Israel Institute of Technology & Technion Faculty of Medicine
Lihi Tzur, Technion Faculty of Medicine
Shoshana Roizman, Technion Faculty of Medicine
Ilanit Boyango, Technion Faculty of Medicine
Gil Bar-Sela, Technion Israel Institute of Technology & Technion Faculty of Medicine
Amir Orian, Technion Israel Institute of technology
Randal J. Kaufman, Sanford Burnham Prebys Medical Discovery Institute
Marcus Bosenberg, Yale University
Colin R. Goding, Unviversity of Oxford
Bas Baaten, Sanford Burnham Prebys Medical Discovery Institute
Mitchell P. Levesque, University of Zurich
Reinhard Dummer, University of Zurich
Kevin Brown, National Cancer Institute
Glenn Merlino, National Institutes of Health
Eytan Ruppin, University of Maryland & Tel Aviv University & National Institutes of Health
Keith Flaherty, Harvard Medical School
Amanda Ramer-Tait, University of Nebraska- Lincoln
Tao Long, Sanford Burnham Prebys Medical Discovery Institute
Scott N. Peterson, Sanford Burnham Prebys Medical Discovery Institute
Linda M. Bradley, Sanford Burnham Prebys Medical Discovery Institute
Ze’ev A. Ronai, Sanford Burnham Prebys Medical Discovery Institute & Technion Israel Institute of TechnologyFollow

ORCID IDs

http://orcid.org/0000-0002-8916-7303

http://orcid.org/0000-0002-8189-5939

http://orcid.org/0000-0003-4277-316X

http://orcid.org/0000-0002-1614-3909

http://orcid.org/0000-0002-8558-6711

http://orcid.org/0000-0002-3402-0478

http://orcid.org/0000-0003-0950-7548

http://orcid.org/0000-0002-7052-9546

Date of this Version

2019

Citation

NATURE COMMUNICATIONS | (2019) 10:1492 | https://doi.org/10.1038/s41467-019-09525-y | www.nature.com/naturecommunications

Comments

The Author(s) 2019

Abstract

Accumulating evidence points to an important role for the gut microbiome in anti-tumor immunity. Here, we show that altered intestinal microbiota contributes to anti-tumor immunity, limiting tumor expansion. Mice lacking the ubiquitin ligase RNF5 exhibit attenuated activation of the unfolded protein response (UPR) components, which coincides with increased expression of inflammasome components, recruitment and activation of dendritic cells and reduced expression of antimicrobial peptides in intestinal epithelial cells. Reduced UPR expression is also seen in murine and human melanoma tumor specimens that responded to immune checkpoint therapy. Co-housing of Rnf5−/− and WT mice abolishes the anti-tumor immunity and tumor inhibition phenotype, whereas transfer of 11 bacterial strains, including B. rodentium, enriched in Rnf5−/− mice, establishes anti-tumor immunity and restricts melanoma growth in germ-free WT mice. Altered UPR signaling, exemplified in Rnf5−/− mice, coincides with altered gut microbiota composition and anti-tumor immunity to control melanoma growth.

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