Glutamine synthetase loss in β-catenin–mutant hepatocellular carcinoma promotes tumor burden through macrophage metabolic reprogramming

We demonstrate the unique metabolic dependency of β-catenin-mutated HCCs on GS in tumor cells, which is diverted to macrophages upon GS elimination in tumor cells. This adaptation alters macrophage metabolism and function, leading to compromised immunosurveillance and greater tumor burden. Our study reveals a metabolic dynamic between HCC cells and macrophages with an impact on tumor biology.