Fig. 2.

Immunogenicity of MCC. a MCCs can be divided upon their association with MCPyV. For both, viral and non-viral MCCs, the cell of origin has not yet been identified and, consequently, it is currently not known if they originate from the same cell. Although transformation is caused by the virus or by UV-induced mutations, they both lead to RB and p53 pathway inactivation. Immunogenicity of both tumors is high due to presentation of viral peptides or neoantigens, respectively [47]. b Based on programmed death-ligand 1 (PD-L1) expression and immune infiltrate, non-viral MCC cases can be divided into immune-resistant or immune-ignorant tumors. The latter demonstrate a lower mutagenic burden [47]. c MCC tumors present with a low/absent expression of the stress molecules MHC class I polypeptide-related sequence A and B (MICA/B). Treatment of MCC cells with histone deacetylases leads to induction/increased expression of MICA/B [8]. These natural killer group 2D (NKG2D) ligands act co-stimulatory on T cells and activate on NK cells. Consequently, the lysis of tumor cells by immune cells is increased after histone acetylase inhibition