Guillaume is investigating the immunosurveillance mechanisms of colorectal tumors. Patients with DNA mismatch repair deficiency (MMRd) have an 80% increased risk for developing microsatellite unstable (MSI-H) cancers (colon, endometrial, ovarian) with a germline prevalence of 1 in 320 individuals. MMRd tumors are highly immunogenic, characterized by elevated mutational burden and T cell infiltration, yet tumors may escape from immune surveillance. Although anti-PD-1 therapy is highly effective, 50% of MMRd and most MMR proficient colorectal cancer patients do not respond. Therefore, it is critical to investigate the immune escape mechanisms that occur during tumorigenesis and after anti-PD-1 failure. His goal is to elucidate the resistance mechanisms of colorectal tumors during development, after anti-PD-1 therapy, and to design new strategies to overcome resistance. He also decipher mechanisms of tumor immunosurveillance that are conserved across the evolution in different species. He uses murine colorectal models, 3D patient derived tumor spheroid models, vaccination approaches and various myeloid and T cell checkpoint blockades to address these objectives.
