Abstract IA22: The unsuspected role of gut microbiota in cancer therapies: Antigen mimicry between intestinal phage and tumor antigens

Abstract

Abstract We recently highlighted the crucial role of gut microbiota in eliciting innate and adaptive immune responses beneficial for the host in the context of effective therapies against cancer. Chemotherapeutic agents facilitate the gut permeability and selective translocation of gram-positive bacteria in secondary lymphoid organs. There, anticommensal pathogenic TH17 T-cell responses are primed, facilitating the accumulation of TH1 helper T cells in tumor beds post-chemotherapy as well as tumor regression (Viaud, Science 2013). These findings have been extended to platinum salts as well as to a combination of anti-IL-10R mAb+CpG (Iida et al., Science 2013 Nov). The immune checkpoint blockers (ICB) anti-CTLA4 Ab and anti-PD1/PD-L1 Ab are first-in-class compounds approved for reinstating cancer immunosurveillance and prolonging survival in metastatic patients. Zitvogel’s group showed that antibiotics compromise the efficacy of these ICB in mice and patients and unveiled the immunomodulatory role of distinct commensals from the intestinal ecosystem in mobilizing anticancer immunosurveillance. Vétizou et al. showed that the antitumor effects of CTLA4 blockade, largely dependent upon Toll-like receptor (TLR)2/TLR4 receptors, markedly rely on the regulatory commensal Bacteroides fragilis (in coordination with Burkholderia cenocepacia; Science 2015 Nov). Next, the demonstration of the deleterious role of antibiotics in the clinical efficacy of PD-1 blockade in lung, kidney, and bladder cancer patients was brought up, highlighting the role of Akkermansia muciniphila as the main player in the immunomodulatory effects of pembrolizumab or nivolumab (Routy et al., Science 2017 Nov 2). The mechanisms by which distinct microbes restoring gut dysbiosis can mediate antitumor effects will be uncovered, including the demonstration of antigen mimicry between intestinal phages and tumor antigens. From these findings, we infer that oncomicrobiotics and/or fecal microbial transplantation could be considered as adjuvants to the current oncologic armamentarium in dysbiotic cancer bearers. Citation Format: Laurence Zitvogel. The unsuspected role of gut microbiota in cancer therapies: Antigen mimicry between intestinal phage and tumor antigens [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA22.