TY - JOUR AU - Uribe-Herranz, Mireia AU - Rafail, Stavros AU - Beghi, Silvia AU - Gil-de-Gómez, Luis AU - Verginadis, Ioannis AU - Bittinger, Kyle AU - Pustylnikov, Sergey AU - Pierini, Stefano AU - Perales-Linares, Renzo AU - Blair, Ian A. AU - Mesaros, Clementina A. AU - Snyder, Nathaniel W. AU - Bushman, Frederic AU - Koumenis, Constantinos AU - Facciabene, Andrea T1 - Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response PY - 2020/01/02/ AB - 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. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI124332 VL - 130 IS - 1 UR - https://doi.org/10.1172/JCI124332 SP - 466 EP - 479 PB - The American Society for Clinical Investigation ER -