In a cohort of HCC clinical samples, the authors highlighted the role of the cardiotrophin-like cytokine factor 1 (CLCF1)-CXCL6/TGF-β axis in the regulation of cancer stemness, alongside the concomitant recruitment of “N2” TANs, contributing to the poor prognosis of HCC patients. Here, CXCL6 is linked to hepatocellular carcinoma.