A3B and A3BE68Q/E255Q-expressed proteins interact with polycomb repressor complex 2 (PRC2) and regulate H3K27me3-mediated chemokine CCL2 to recruit massive TAMs and MDSCs, suggesting a deaminase-independent role of the A3B in modulating the HCC microenvironment. This evidence concerns the gene APOBEC3B and hepatocellular carcinoma.