*5.6. Microsatellite-Unstable Tumours*

As described above, it is believed that the set of neoantigens in a tumour is highly individual. This characteristic is what differentiates them from tissue-specific antigens, tumour-associated antigens (TAAs) or other tumour-selective antigens that are considered to be shared. The exception to this is some cancers that possess a high mutational load, including microsatellite-unstable tumours, which have shared neo-antigens due to preferential mutations of several genetic regions called microsatellites.

Cancers with hereditary defects in genes involved in DNA repair have high frequencies of non-synonymous mutations, resulting in a wide variety of tumour neoantigens. In some cases, insertions and deletions also accumulate in DNA hot spots that are prone to mutations with repeating base-pair sequences, called microsatellite instability (MSI). This has made it possible to identify genes with a high mutation frequency in patients with MSI. These recurrent neoantigens can be prime targets for immunotherapy, particularly frame-shifting mutations containing multiple new epitopes that are recognised by several MHC haplotypes [348]. Patients with these types of defects are highly mutational and therefore form immune escape variants. Defects in antigenic presentation by MHC molecules and in molecules associated with MHC expression have been found in patients with MSI tumours [349]. Unstable microsatellite tumours are recognised as a subset of tumours with different prognostic and predictive characteristics.
