Targeting MDM2-induced p53 downregulation to enhance anti-leukaemia immunity

Project Summary

Based on our preliminary data we will analyse how reduced expression of the tumour suppressor p53 promotes immune evasion in leukaemia after allo-HCT. Therefore 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. p53-mediated activation of promoters of immune related genes will be assessed in mouse and human AML cells. Thirdly, resistance mechanisms in AML which preventimmune related gene 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.