Immunoediting in cancer evolution

Our antigen repertoire determines the recognition of our own cells by the immune system as “self”. As soon as the antigen repertoire of a cell changes, be it due to viral infection or tumor development, the immune system can recognize those novel antigens as “foreign” and eliminate the affected cell.

Not all tumors carry such novel antigens, and therefore, the recognition of a tumor by the immune system often fails. Microsatellite-unstable (MSI) tumors are unique with regard to their antigenicity, as the mutations accumulating during MSI tumor evolution lead to an extremely high amount of such novel neoantigens, enabling their recognition. Therefore, MSI cancers being under strong immune selective pressure often develop mechanisms of immune evasion. The most common mechanism of immune evasion in MSI tumors is related to antigen presentation. This could be either reflected in the emergence of cell clones with a complete loss of certain molecules of the antigen presentation machinery (including HLA molecules), or cell clones carrying preferentially the antigens not fitting into the given HLA pockets, and thereby ensuring tumor invisibility for the immune system.