TNF and hepatocellular carcinoma: Hepatic stellate cells promote sorafenib resistance in HCC cells through the laminin-332/α3 integrin axis, which enables FAK to escape sorafenib-induced ubiquitination.328 In HCC, CAFs activate the IL-6/STAT3 pathway in neutrophils, inducing the expression of PD-L1, TNF-α, IL-8, and CCL2, which impair T-cell function via the PD-1/PD-L1 axis.329 CAFs also secrete cardiotrophin-like cytokine factor 1 (CLCF1), stimulating HCC cells to release CXCL6 and TGF-β, thereby increasing tumor stemness and promoting TAN infiltration and polarization.330