Objectif The tumour microenvironment or niche is the vital non-cancerous compartment of the tumour structure. Thus, targeting its tissue-derived cells represents a promising avenue to better therapeutic interventions. However, knowledge about the tissue cells taking part of the tumour niche during early cancer development and later progression is lagging behind due to the difficulty of analysing and following early tissue changes in the surrounding of cancer cells in vivo. In our research proposal we will use a combination of original tools developed in the lab and state of the art technologies to overcome some of these constraints and expand our understanding of which cells in the niche support early cancer cell growth. We also aim to reveal their mechanism of action and identify approaches to block the niche supportive activity. Our five-year plan has three main objectives (I, II, III), which we will meet using two original strategies. With the first strategy we will visualize the early tumourigenic niche in vivo. This will allow us (I) to identify and characterize novel cellular components during dynamic niche evolution both in the context of metastatic colonization as well as during primary tumour onset. We will also use this original approach (II) to deepen our understanding of neutrophils in cancer, a particularly crucial emerging component of the cancer niche, whose role is still debated. After dissemination, cancer cells may encounter an unfavourable niche, failing to start colonization and remaining dormant within the tissue. However, the quiescent-permissive tissue can change, cancer cells reactivate and form metastases even a long period after tumour resection. Little is known about the changes in the niche of dormant cells capable of triggering their reactivation. With the second strategy we will generate an in vivo a controllable, dormant-permissive tissue (III) to screen for potential signals triggering dormant cells reactivation. Champ scientifique medical and health sciencesclinical medicineoncology Mots‑clés Tumour microenvironment Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-COG - ERC Consolidator Grant Appel à propositions ERC-2016-COG Voir d’autres projets de cet appel Régime de financement ERC-COG - Consolidator Grant Institution d’accueil THE FRANCIS CRICK INSTITUTE LIMITED Contribution nette de l'UE € 2 000 000,00 Adresse 1 MIDLAND ROAD NW1 1AT London Royaume-Uni Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 000 000,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire THE FRANCIS CRICK INSTITUTE LIMITED Royaume-Uni Contribution nette de l'UE € 2 000 000,00 Adresse 1 MIDLAND ROAD NW1 1AT London Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 2 000 000,00