Project Summary
P17 investigates if vertical RAS+SHP2 blockade can sensitize PDAC to immunotherapy. Aim 1 is dedicated to identifying immune architectures in human and murine PDAC tissues, with correlation to genetic setup, i.e. mutated KRAS and major tumour suppressor loss. Aim 2 assesses the impact of RAS+SHP2 inhibition on signalling and expression of immunoregulators in PDAC organoids and cell lines, and profiles off-target immune cell specific effects. Based on preliminary data, Aim 3 tests the addition of TGFβR1i/anti-TIM-3 (anti-TIGIT) to vertical RAS+SHP2 blockade in murine and human tumours.
