Journal article
Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
The Journal of clinical investigation, v 130(1), pp 466-479
01 Jan 2020
PMID: 31815742
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8(+) T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic CD8(+) T cells and on IFN-gamma. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.
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Details
- Title
- Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
- Creators
- Mireia Uribe-Herranz - University of PennsylvaniaStavros Rafail - University of PennsylvaniaSilvia Beghi - Department of Radiation Oncology and.Luis Gil-de-Gomez - Department of Radiation Oncology and.Ioannis Verginadis - Department of Radiation Oncology and.Kyle Bittinger - Children's Hospital of PhiladelphiaSergey Pustylnikov - Department of Radiation Oncology and.Stefano Pierini - University of PennsylvaniaRenzo Perales-Linares - Department of Radiation Oncology and.Ian A. Blair - University of PennsylvaniaClementina A. Mesaros - University of PennsylvaniaNathaniel W. Snyder - Center for Autism and Related DisordersFrederic Bushman - University of PennsylvaniaConstantinos Koumenis - Department of Radiation Oncology and.Andrea Facciabene - University of Pennsylvania
- Publication Details
- The Journal of clinical investigation, v 130(1), pp 466-479
- Publisher
- Amer Soc Clinical Investigation Inc
- Number of pages
- 14
- Grant note
- 1R01CA219871-01A1 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000505205000045
- Scopus ID
- 2-s2.0-85077402591
- Other Identifier
- 991019168114304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medicine, Research & Experimental