TY - JOUR
T1 - Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response
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
N1 - Publisher Copyright:
© 2020, American Society for Clinical Investigation.
PY - 2020/1/2
Y1 - 2020/1/2
N2 - 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 grampositive 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.
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 grampositive 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.
UR - http://www.scopus.com/inward/record.url?scp=85077402591&partnerID=8YFLogxK
U2 - 10.1172/JCI124332
DO - 10.1172/JCI124332
M3 - Article
C2 - 31815742
AN - SCOPUS:85077402591
SN - 0021-9738
VL - 130
SP - 466
EP - 479
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 1
ER -
