The Immune Biology of Microsatellite-Unstable Cancer

Deficient DNA mismatch repair (MMR) boosts the accumulation of frameshift mutations in genes encompassing coding microsatellites (cMS). This results in the translation of proteins with mutation-induced frameshift peptides (neoantigens) rendering microsatellite-unstable (MSI) cancers highly immunogenic. MSI cancers express a defined set of neoantigens resulting from functionally relevant driver mutations, which are shared by most MSI cancers. Patients with MSI cancers and healthy individuals affected by Lynch syndrome, an inherited predisposition for MSI cancers, develop specific immune responses against these neoantigens. In this review, we summarize our current understanding of the immune biology of MSI cancers and outline new concepts and research directions to develop not only therapeutic treatments, but also preventive vaccines based on the MSI cancer genome landscapes.