Targeting KRAS-driven tumours via their dependence on PTPN11/SHP2-phosphatase to enhance anti-tumour immunity (P17)

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

P17 will assess if dampening oncogenic KRAS signalling output via SHP2- and MEK-inhibition can reverse the immunosuppressive properties of mutant KRAS in pancreatic cancer and colorectal cancer. This approach relies on the previous finding by the PI that adequate function of mutant KRAS depends on presence and activity of the tyrosine phosphatase SHP2, encoded by PTPN11. In a translational approach, P17 will use KRAS mutant syngeneic murine and human PTPN11 knockout tumor models to identify immunotherapeutic vulnerabilities. Further, P17 will elaborate the impact of SHP2- and MEK-inhibition on tumor-associated macrophages and CD4-T-cell subsets in vivo.

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