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Introduction Radiotherapy (RT) is a well-established antitumor treatment, with more than 50% of newly diagnosed cancer patients with solid tumors receiving RT at some point during their treatment, usually in [...], 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.sup.+] 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.sup.+] 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.

Introduction Angiogenesis, the growth of new blood vessels from preexisting vessels, is essential for many physiological processes, such as pregnancy, embryonic development, and wound healing (1). However, uncontrolled or defective [...], Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Teml cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited [CD8.sup.+] and/or [CD4.sup.+] T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization ofanimals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of [CD3.sup.+] T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited [CD8.sup.+] cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy.