A study by Yang et al. on mice HCC models proposed 17-βestradiol as an agent that is able to suppress macrophage alternative activation, directing macrophage differentiation from M2-type to M1-type, consequently inhibiting HCC progression and decreasing its growth and metastatic spread through the enhancement of anti-neoplastic immune response and local vascular normalization [54]: its mechanism of action consists in preventing the interaction between estrogen-receptor ERβ and ATP-ase-coupling factor 2, with the subsequent inhibition of the signaling pathway JAK1-STAT6. This evidence concerns the gene JAK1 and hepatocellular carcinoma.