Counteracting NRAS- and c-KIT-driven immune escape in AML by kinase inhibition and T-cell reprogramming

In P01 we plan to investigate whether inhibition of oncogenic signalling in c-KIT-D816V- and NRAS-G12D-driven AML models can induce T-cell reprogramming by reducing immunosuppressive CD155, Gal-9 and adenosine. Aim 2 is dedicated to the discovery of signalling events and transcription factors downstream of c-KIT-D816V and NRAS-G12D that cause CD155, Gal-9 and CD73 expression, whereas MHC-II expression is reduced. In Aim 3 we will validate the findings from mouse models in human AML cells that carry c-KIT-D816V, NRAS-G12D using scRNA-seq, proteomics and metabolomics approaches.