Using the AKT/NICD ICC model,15 we demonstrate additional LTβR-specific molecular changes occur in association with upregulation of c-MYC,38 cyclin D1, cyclin E139 and CAT.40, 41 It remains uncertain if these oncogenic proteins are directly regulated by LTβR signalling or indirectly induced by factors in the microenvironment. This evidence concerns the gene AKT1 and intrahepatic cholangiocarcinoma.