MSI cancers show high lymphocyte infiltration. We were able to demonstrate that the local immune responses against MSI tumors are paralleled by pronounced systemic immune responses. In blood samples isolated from Lynch syndrome patients with MSI cancer, we identified T cells that specifically recognize FSP neoantigens. Interestingly, in blood samples from Lynch syndrome patients who have never had a tumor, FSP-specific T cells were detected as well. This finding led us to the discovery of MMR-repair deficient crypt foci, a novel colorectal cancer precursor in Lynch syndrome.
The existence of immune responses against FSP neoantigens in healthy Lynch syndrome individuals reflects a continuous process of auto-vaccination in Lynch syndrome individuals. We are currently initiating a project to systematically monitor T cell responses in Lynch syndrome individuals over time and in dependence of tumor status.