Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
(1) Uribe-Herranz M (2) Rafail S (3) Beghi S (4) Gil-de-Gomez L (5) Verginadis I (6) Bittinger K (7) Pustylnikov S (8) Pierini S (9) Perales-Linares R (10) Blair IA (11) Mesaros CA (12) Snyder NW (13) Bushman F (14) Koumenis C (15) Facciabene A
(1) Uribe-Herranz M (2) Rafail S (3) Beghi S (4) Gil-de-Gomez L (5) Verginadis I (6) Bittinger K (7) Pustylnikov S (8) Pierini S (9) Perales-Linares R (10) Blair IA (11) Mesaros CA (12) Snyder NW (13) Bushman F (14) Koumenis C (15) Facciabene A
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.
Author Info:
(1) Department of Radiation Oncology and. Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (2) Ovarian Canc
er Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (3) Department of Radiation Oncology and. (4) Department of Radiation Oncology and. (5) Department of Radiation Oncology and. (6) Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. (7) Department of Radiation Oncology and. (8) Department of Radiation Oncology and. Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (9) Department of Radiation Oncology and. (10) Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (11) Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (12) AJ Drexel Autism Institute, Philadelphia, Pennsylvania, USA. (13) Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. (14) Department of Radiation Oncology and. (15) Department of Radiation Oncology and. Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
