Understanding the crosstalk between juvenile myelomonocytic leukaemia (JMML) and immune cells

Project Summary

We aim to unveil mechanisms driving immune escape of JMML with PTPN11 or KRAS mutations to identify novel therapeutic approaches. First, we will investigate immune checkpoints molecules by gene and protein expression profiling caused by oncogenic signalling in murine JMML models with defined signalling alterations based on genetic loss-of-function and pharmacological approaches. Second, we will characterize the immune escape mechanisms in human primary JMML samples using deep immune profiling. Third, we will test if we can prevent JMML relapse in mice by interfering with immune escape mechanisms when combining targeted immunotherapies with inhibitors of oncogenic signalling.