First evidence that neoepitopes resulting from non-synonymous mutations are recognized by the immune system as “altered self” was provided by Wölfel et al. The authors identified a p16INK4a-insensitive cyclin-dependent kinase 4 (CDK4)-R24C mutation in melanoma patients as a neoantigen that was a target of CTL responses (38). Here, CDK4 is linked to melanoma.