Title: Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response.
Authors: Uribe-Herranz, Mireia; Rafail, Stavros; Beghi, Silvia; Gil-de-Gómez, Luis; Verginadis, Ioannis; Bittinger, Kyle; Pustylnikov, Sergey; Pierini, Stefano; Perales-Linares, Renzo; Blair, Ian A; Mesaros, Clementina A; Snyder, Nathaniel W; Bushman, Frederic; Koumenis, Constantinos; Facciabene, Andrea
Published In J Clin Invest, (2020 01 02)
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-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.
PubMed ID:
31815742
MeSH Terms: Animals; Antigen Presentation/genetics; Antigen Presentation/radiation effects*; Antigens, Neoplasm/genetics; Antigens, Neoplasm/immunology*; Butyrates/immunology; CD8-Positive T-Lymphocytes/immunology*; CD8-Positive T-Lymphocytes/pathology; Dendritic Cells/immunology*; Dendritic Cells/pathology; Female; Gastrointestinal Microbiome*/immunology; Gastrointestinal Microbiome*/radiation effects; Mice; Mice, Knockout; Neoplasms, Experimental*/genetics; Neoplasms, Experimental*/immunology; Neoplasms, Experimental*/pathology; Neoplasms, Experimental*/radiotherapy