Abstract 666: Gut microbiota SCFA modulates DCs antigen presentation and impacts tumor response to radiotherapy

Alterations in gut microbiota modulate host physiologic functions, including immune responses, and they play a role in 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. Herein, we tested whether the gut microbiota modulates antitumor immune response following RT. 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 tumor-associated antigen cross-presentation enanchement, cytolytic CD8+ T cells and on IFN-g. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, gram-positive bacteria depletion by vancomycin enhances the antitumor activity of RT, which has important clinical ramifications. Citation Format: Andrea Facciabene, Stavros Rafail, Luis Gil de Gomez, Stefano Pierini, Mireia Uribe-Herranz, Kyle Bittinger. Gut microbiota SCFA modulates DCs antigen presentation and impacts tumor response to radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 666.