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Nat Commun. 2019 Apr 2;10(1):1492. doi: 10.1038/s41467-019-09525-y.

Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5-/- mice.

Author information

1
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
2
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA.
3
Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA.
4
Center for Bioinformatics and Computational Biology, Department of Computer Science, University of Maryland, College Park, MD, 20742, USA.
5
School of Computer Sciences and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
6
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
7
Technion Integrated Cancer Center, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, 31096, Israel.
8
Division of Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, 02114, USA.
9
Department of Computer Science, College of Engineering and Computer Science, University of Central Florida, Orlando, FL, 32816, USA.
10
BioLegend, San Diego, CA, 92121, USA.
11
Division of Cancer Epidemiology and Genetics, Laboratory of Translational Genomics, National Cancer Institute, Bethesda, MD, 20892, USA.
12
Departments of Dermatology and Oncology, Rambam Health Care Campus, Technion Faculty of Medicine, Haifa, 31096, Israel.
13
Department of Pathology, Yale University, New Haven, CT, USA.
14
Ludwig Institute for Cancer Research, Nuffield Department of Medicine, Old Road Campus, Unviversity of Oxford, Headington, Oxford, OX3 7DQ, UK.
15
Department of Dermatology, University Hospital of Zurich and University of Zurich, 8091, Zurich, Switzerland.
16
Cancer Data Science Lab, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
17
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. zeev@ronailab.net.
18
Technion Integrated Cancer Center, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, 31096, Israel. zeev@ronailab.net.

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.

PMID:
30940817
PMCID:
PMC6445090
DOI:
10.1038/s41467-019-09525-y
[Indexed for MEDLINE]
Free PMC Article

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