Targetable modifiers of T cell exclusion in KrasG12D -driven colorectal cancer

Project Summary

To understand the mechanism of immune evasion depending on the oncogene and other factors to overcome the limitations of current immunotherapies we will perform in vivo screens using cellular systems harbouring colorectal cancer driver mutations that allow in vivo analysis in immunecompetent mice. To clarify which oncogenes cause resistance to ICB, we will use organoids with or without oncogenic KrasG12D or intact p53 and then study responses. Individual candidates from the initial screen will be finally validated using single sgRNAs in combination with ICB therapy in appropriate colorectal cancer mouse models.