These results suggest that an expanded CD19+CD24+CD38+ peripheral blood Breg population in patients with HCC may migrate to the tumor margin and mediate tumor growth via local elaboration of immunosuppressive cytokines IL-10 and TGF-β, dependent on cognate interactions between CD40L and CD40 on Bregs and HCC cells respectively. The gene discussed is CD40; the disease is hepatocellular carcinoma.