LCA (and its high affinity conjugate TLCA) as a strong TGR5 agonist activates cAMP → STAT3/STAT6 and the inflammatory immunosuppressive pathway in the liver that bias macrophages toward immunosuppressive states, which establishes a pro-tumor microenvironment conducive to HCC progression [48, 191]. Here, STAT3 is linked to hepatocellular carcinoma.