Theme 1: Sensing of the gut microbiota by antigen presenting cells for control of immune response to cancer cells and discovery of potent antitumoral vaccine targets (P.I. LF. Poulin). Dr LF. Poulin aims at understanding how phagocytes may regulate tolerance to the gut microbiota and tumor immune surveillance with a specific interest on the myeloid commitment shift. Understanding this paradigm is of importance because the plasticity of the tumor microenvironment influences therapeutic resistance. This led us to unveil an unexpected function of the periodic fever Nlrp12 gene as a checkpoint inhibitor of NOD2 signalling in monocytes for maintenance of bacterial tolerance and host defence (PMID:30279238, Normand et al., Nat Commun. in Press and a declaration of invention EP14306662). Encouraged by these results, our most recent work paid off by the identification of two additional regulatory pathways of NOD2 signalling that are required for the development of monocyte-derived dendritic cells (Chauvin et al., manuscript in preparation and PMID:29209091). In this context, an international patent application has been filed with Inserm-Transfert for controlling monocytopoiesis (EP17305990).
Theme 2: Gut microbiota, epithelial permeability and clinical efficacy of antitumoral drugs and radiotherapies (P.I. M. Chamaillard). Despite an extensive research on the interplay between chronic inflammation and development of cancer, it is now a prerequisite to understand the cause of heterogeneity on responsiveness to antitumoral drugs and radiotherapies. In recent years, a major conceptual advance has emerged in our understanding of the factors that modulate the efficacy of anti-cancer immunomodulatory agents. Our preliminary studies have more recently underlined that it also relies on the epithelial permeability (PMID:27717798). In this context, our central hypothesis is that dysregulation of gut barrier function synergizes with cancer treatments (such as radiation therapy and some antineoplastic agents) to enhance anti-tumoral immunity and particularly response to immune checkpoint blockade. An international patent application has been filed with Inserm Transfert for improving the resilience of the gut microbiota by the use of flavones (WO2017198847A1).