DNMT1 and DNMT3b may cooperatively maintain mDNA and gene silencing in cancer cells, synergizing their biological function, improving methylation efficacy, and suppressing PD-L1 expression more efficiently than DNMT3ac alone; this hypothesis was supported by pre-clinical studies using recombinant constructs (expressing the C-terminal domains of DNMT3a and/or DNMT1 fused with a zinc finger domain specifically binding to the PD-L1 promoter) [7]. This evidence concerns the gene DNMT3A and cancer.