Immune pressures drive the promoter hypermethylation of neoantigen genes.

Cancer cells with strong immunogenicity are susceptible for elimination by cancer immunoediting, while the subpopulations with weak immunogenicity survive. As a result, a subset of cancer cells evade the immune attack and evolve into overt clinical lesions. During cancer evolution, it has been well established that multiple alterations such as the dysfunction of antigen presentation machinery and the upregulation of immunosuppressive signals (e.g. PD-L1) play important roles in immune escape. Recently, promoter hypermethylation of neoantigen genes has been proposed to be a vital mechanism of immunoediting. This epigenetically mediated immune evasion enriches the mechanisms of carcinogenesis.