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Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
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Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
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Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
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Journal Article
Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
2020
Overview
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-γ. 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.
Publisher
American Society for Clinical Investigation
Subject
/ Antigen Presentation - genetics
/ Antigen Presentation - radiation effects
/ Antigens
/ Antigens, Neoplasm - genetics
/ Antigens, Neoplasm - immunology
/ Bacteria
/ Cancer
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - pathology
/ Dendritic Cells - immunology
/ Diseases
/ Esters
/ Female
/ Gastrointestinal Microbiome - immunology
/ Gastrointestinal Microbiome - radiation effects
/ Melanoma
/ Mice
/ Microbiota (Symbiotic organisms)
/ Neoplasms, Experimental - genetics
/ Neoplasms, Experimental - immunology
/ Neoplasms, Experimental - pathology
/ Neoplasms, Experimental - radiotherapy
/ Scientific equipment industry
/ T cells
/ Tumors
