In hepatocellular carcinoma (HCC), exosomal HMGB1 activates B cells with suppressive activity against CD8+ T cells and promotes TIM-1+ Breg cell expansion via the Toll-like receptor (TLR)2/4 and mitogen-activated protein kinase (MAPK) signaling pathways (25). This evidence concerns the gene CD8A and hepatocellular carcinoma.