Fig. 1

Promoter hypermethylation-mediated neoantigen downregulation leads to evasion of cancer immune response. Release of abundant neoantigens initiate anti-cancer immune response. Then, professional antigen presentation cells (APCs) take in and process these neoantigens. Subsequently, in peripheral lymphoid organs, the naïve T lymphocytes are primed and activated by APCs. These activated T cells migrate and infiltrate into tumors (TILs). These TILs recognize and destroy cancer cells. As a result, more neoantigens propagate the anti-cancer immune response. Under these immune pressure, cancer cells downregulate neoantigen expression by promoter hypermethylation and evolve into weakly immunogenic subclones