Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
- 9 December 2019
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (1), 466-479
- https://doi.org/10.1172/jci124332
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.This publication has 78 references indexed in Scilit:
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