Mechanisms and therapeutic strategies of gut microbiota in the immune‑suppressive micro-environment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the third leading cause of cancer‑related death worldwide, has limited treatment options and poor prognosis for advanced patients. The tumor microenvironment of HCC is characterized by significant immune‑suppressive features, primarily manifested through the expansion of myeloid‑derived suppressor cells, increased infiltration of regulatory T cells, and polarization of tumor‑associated macrophages towards the M2 phenotype. These alterations collectively promote immune evasion and diminish the efficacy of immuno-therapies. Recent studies have revealed that gut microbiota dysbiosis plays a crucial role in shaping the immune‑suppressive microenvironment of HCC via the gut‑liver axis. Furthermore, intervention strategies targeting gut microbiota dysbiosis have demonstrated potential therapeutic value. However, the molecular mechanisms by which the gut microbiota regulates the formation of HCC immune-suppressive microenvironment are heterogeneous, and clinical translation faces numerous challenges that require further investigation. The authors review comprehensively the mechanisms by which gut microbiota dysbiosis regulates the immune‑suppressive tumor microenvironment in HCC, sum-marize the latest advances in related therapeutic strategies, and provide an outlook on their clinical application. The aim is to offer new theoretical foundations and potential therapeutic targets for HCC immunotherapy.