Overcoming immune evasion of BRAF mutant colorectal cancer

Project Summary

Our unpublished data imply that BRAFV600E triggers various immune escape mechanisms in colorectal cancer. We will test the hypothesis that clinically applied inhibitors of the BRAF/MEK/ERK axis could improve the recognition and elimination of colorectal cancers by cytotoxic T and NK cells, and the efficacy of immune checkpoint therapies. We will test this concept using heterotypic colon organoid cultures containing immune cells, a fully immune competent mouse model expressing BRAFV600E in the colon, and human tumour samples. With this work program, we aim to provide novel therapeutic strategies overcoming immune escape of the aggressive BRAFV600E-mutant colorectal cancer subtype.