Obiettivo CD8+ T cells have a key role in eliminating intracellular pathogens and tumors that affect the liver. The protective capacity of these cells relies on their ability to migrate to and traffic within the liver, recognize pathogen- or tumor-derived antigens, get activated and deploy effector functions. While some of the rules that characterize CD8+ T cell behavior in the infected and cancerous liver have been characterized at the population level, we have only limited knowledge of the precise dynamics of intrahepatic CD8+ T cell conduct at the single-cell level. In preliminary data for this project we have developed several advanced imaging techniques that allow us to dissect the interactive behavior of CD8+ T cells within the mouse liver at an unprecedented level of spatial and temporal resolution. We predict that this approach, combined with unique models of hepatitis B virus pathogenesis and a new model of hepatocellular carcinoma created ad hoc for this proposal, will generate novel mechanistic insights into the spatiotemporal determinants that govern the capacity of CD8+ T cells to home and function in the virus- or tumor-bearing liver. Specifically, we plan to pursue two main goals: 1) To assess how the anatomical, hemodynamic and environmental cues that characterize hepatocellular carcinomas shape CD8+ T cell behavior and function; 2) To characterize intrahepatic T cell priming events that induce functionally defective T cell responses. Results emerging from these studies will advance our knowledge on how adaptive immunity mediates pathogen clearance and tumor elimination. This new knowledge may lead to improved vaccination and treatment strategies for immunotherapy of infectious diseases and cancer. Campo scientifico natural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapy Parole chiave CD8+ T cells Intravital Imaging Dynamics of Immune Responses Liver Hepatitis B Virus Hepatocellular Carcinoma Immunopathology Programma(i) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Argomento(i) ERC-2016-COG - ERC Consolidator Grant Invito a presentare proposte ERC-2016-COG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-COG - Consolidator Grant Istituzione ospitante OSPEDALE SAN RAFFAELE SRL Contribution nette de l'UE € 2 390 000,00 Indirizzo VIA OLGETTINA 60 20132 Milano Italia Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 390 000,00 Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo netto dell'UE Espandi tutto Riduci tutto OSPEDALE SAN RAFFAELE SRL Italia Contribution nette de l'UE € 2 390 000,00 Indirizzo VIA OLGETTINA 60 20132 Milano Mostra sulla mappa Regione Nord-Ovest Lombardia Milano Tipo di attività Private for-profit entities (excluding Higher or Secondary Education Establishments) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Partecipazione a programmi di R&I dell'UE Opens in new window Rete di collaborazione HORIZON Opens in new window Costo totale € 2 390 000,00
