Contribution of the Epstein-Barr Virus and the Tumour Microenvironment to Anti-Apoptotic Mechanisms in DLBCL

ended

Diffuse large B-cell lymphoma (DLBCL) accounts for over one-third of lymphomas and is fatal in up to 40% of cases. Particularly poor survival is associated with DLBCL subtypes that over-express the oncogene MYC and contain the cancer-causing Epstein-Barr virus (EBV). These tumours frequently resist apoptosis, with a poorer response to chemotherapy. Recent evidence has strongly implicated a role for the tumour microenvironment (TME) in cancer progression; however, the relationship between EBV, MYC, and the TME in DLBCL remains poorly understood. CoMAnD aims to elucidate the synergistic relationship between EBV, MYC and the TME to explore how these oncogenic drivers converge to protect DLBCL tumours from apoptosis. This will be achieved using a new generation of EBV+ and EBV- DLBCL models to derive novel insights into the biology of EBV+ DLBCL. This will be coupled with state-of-the-art intravital imaging of tumour progression in humanised mice and highly multiplexed, spatially resolved, imaging of the TME in EBV+/- patient tumours. This will allow the study, in unprecedented detail, of the impact of viral and cellular oncogenic drivers on the TME and apoptosis in DLBCL. This research directly contributes to Cancer- and Infectious disease-related EU and UN goals, and will support the areas of Open Science, Gender Equality, and the Green Charter. The Fellow will spend 2 years at the Walter and Elisa Hall Institute of Medical Research (Australia) expanding her skills in in vitro disease mimetics, and acquiring a skillset in apoptotic pathways and intravital imaging. She will return to the University of Limerick (Ireland) and receive training in high-dimensional imaging and data analytics. The Fellow will be immersed within a multidisciplinary team with expertise in lymphomagenesis, virology, apoptosis and the TME; they will support her in meeting the research/training objectives and preparing for an independent career in the field of EBV-associated lymphomagenesis.