HCC-derived IL-8 induced upon NTS stimulation (i) attracts pro-inflammatory cells (CD28 + macrophages, CD66b + polynuclear neutrophils) to the local microenvironment, triggers an increased formation of pro-inflammatory cytokines and promotes phagocytosis, and (ii) stimulates the polarization of tumor-associated macrophages (TAMs), indirectly promoting EMT and enhances the invasive potential of HCC cells. Here, CD28 is linked to hepatocellular carcinoma.