Studies have shown that both immune and tumor cell‐derived exosomes can modulate HCC progression and immune escape.[26, 27] Specifically, tumor‐derived exosomes can suppress T‐lymphocyte functions, affecting both CD8+ and CD4+ T cells, and disrupting the Th17/Treg balance.[26] In the present study, we demonstrated that HCC‐derived exosomal miR‐500a‐3p could be absorbed by PBMCs, leading to the upregulation of PD‐1 expression and an increase in the proportion of Tregs, which contributed to an immunosuppressive TME. Here, CD4 is linked to hepatocellular carcinoma.