Kumar et al. suggested that the activation of the TLR4/NANOG and leptin receptor (OB-R)/STAT3 signaling pathways in TICs synergize to activate Twist, a potent regulator of EMT, in obesity- and HCV-driven HCC [79], while the activation of TLR4/STAT3 in M2 TAMs influenced EMT in HCC cells, potentiating metastasis. The gene discussed is LEPR; the disease is obesity due to melanocortin 4 receptor deficiency.