Targeting MDM2-induced p53 downregulation to enhance anti-leukaemia immunity (P01)

• Subject Area: Hematology, Oncology ; Rheumatology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 441891347

Based on our preliminary data we will analyse how reduced expression of the tumour suppressor p53 promotes immune evasion in leukaemia after allo-HCT. First, we will assess the functional relevance of p53 modification in vivo by using multiple acute myeloid leukaemia (AML) models, recall immunity approaches and assessment of T cell glycolytic activity. Secondly, p53-mediated activation of MHC-II and IL-15 promoters will be assessed in mouse and human AML cells. Thirdly, resistance mechanisms in AML which prevent MHC-II and IL-15 expression, despite increased p53 levels, will be characterised. Overall we will test the hypothesis that restoring p53 in AML enhances allogeneic anti-AML immune responses.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1479: Oncogene-driven immune escape (OncoEscape)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professor Dr. Robert Zeiser