Objective To summarize mechanisms and research progress of bile acid (BA) regulate the immune microenvironment of hepatocellular carcinoma (HCC) through tumor-associated macrophage (TAM). MethodsRelevant studies published in China and abroad were reviewed, focusing on altered BA metabolism in HCC, BA receptor-mediated changes in TAM function, immune-cell interactions and therapeutic investigations. ResultsAlterations in BA synthesis, conjugation and transport, disrupted microbial transformation can change the composition and tissue distribution of BAs in HCC. Different BAs have different functions such as promoting TAM immunosuppression, enhance antitumor macrophage responses. BA can also directly regulate the functions of CD8+ T cells, natural killer T cells and natural killer cells. Interventions such as targeting BA production, targeting specific BA type and its receptor signaling have reduced tumor burden or enhanced immune therapy effect. Phase Ⅱ studies of BA combined with immune checkpoint inhibitors are in progress. ConclusionsAltered BA composition regulates the HCC immune microenvironment through both TAM and effector lymphocytes, the role of BA determined by its type, receptor, target cell, and disease context. Related mechaniss and therapeutic strategies require further validation in human-derived models and prospective clinical studies.
