LAUSR

The sheer enormity of the microbial biomass in the human intestinal tract, the co-evolution between humans and the microbiota, and the established function of the gut microbes in regulating normal host physiologic functions, are all consistent with the idea that alterations in gut microbial ecology play a role in the pathophysiology of several conditions including cancer. Radiotherapy (RT) is an established curative and palliative cancer treatment regimen, with approximately half of cancer patients with solid tumors receiving RT some time during their disease. Mounting evidence also suggests that high-dose (hypofractionated) radiation exerts potent immune modulatory effects, prompting immunological active tumor cell death inducing tumor associated antigen (TAA) cross priming with elicitation of anti-tumor CD8+ T cells, and abscopal effects. Although there have been groundbreaking responses to immunotherapy in certain malignancies such as lung cancer and melanomas, so far, immunotherapy is effective only in a portion of patients19. This raises the issue of whether there are additional important regulators of T cell function that are relevant to tumor control and could be harnessed to enhance radiotherapy. In support of this hypothesis, we have generated preliminary results demonstrating that: a) Treatment with vancomycin, an antibiotic with action in the gut mostly against Gram+ bacteria, significantly increased the presence of overall tumor infiltrating T cells or cytotoxic CD8+ cells in tumors from mice treated with RT/vancomycin combination compared to RT alone; b) vancomycin caused a significant enhancement of the tumor inhibitory effect of targeted radiation. c) Vancomycin enhanced the ability of RT to increase the expression of IFN-g in CD8+ infiltrating T cells and antigen presentation in the tumor draining lymph nodes and d) the observed synergy between vancomycin and RT in eliciting an anti-tumor immune response and inhibiting tumor growth was abrogated in IFN-g KO animals or by CD8+ cell depletion. Citation Format: Andrea Facciabene, Stavros Rafail, Mireia Uribe-Herranz, Stefano Pierini, Kile Bittinger, Iannis Verginadis, Costas Koumenis, Amit Maity. The impact of the gut microbiome on the antitumor effects of radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-178. doi:10.1158/1538-7445.AM2017-LB-178