Our studies suggest that HCC-CAFs, one of the most important types of tumor stromal cells, can dramatically attract peripheral blood neutrophils via the SDF1a/CXCR4 signaling pathway, and induce their differentiation into PDL1+ neutrophils with a capacity to inhibit T-cell immunity through the IL6-STAT3-PDL1 signaling cascade, which presents a novel mechanism mediating neutrophil activation and function. Here, CXCR4 is linked to hepatocellular carcinoma.