Resistance of the stable—towards more precise prediction of response to immune checkpoint blockade in microsatellite-unstable cancer patients

The introduction of immune checkpoint blockade into the clinical practice has marked a milestone for treating patients with advanced microsatellite-unstable (MSI) cancer (1,2). MSI tumors are evolving with a deficiency of the DNA mismatch repair (MMR) system and therefore accumulate numerous somatic mutations during every cell division, resulting in a very high mutational load in the manifest tumors (3,4). The majority of these mutations seem to affect short repetitive sequence stretches (microsatellites) as insertion or, mostly, deletion of single nucleotides. When microsatellites located in gene-encoding regions are affected by indel mutations, translational frame shifts occur, a process that can give rise to the generation of mutational neoantigens (5,6)