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Publication : Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5<sup>-/-</sup> mice.

First Author  Li Y Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  1492
PubMed ID  30940817 Mgi Jnum  J:275027
Mgi Id  MGI:6287017 Doi  10.1038/s41467-019-09525-y
Citation  Li Y, et al. (2019) Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5(-/-) mice. Nat Commun 10(1):1492
abstractText  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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