Short‑chain fatty acids regulate hepatocellular carcinoma progression: A metabolic perspective on tumor immunity (Review).

Abstract

Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide and is characterized by complex metabolic and immunological processes throughout its progression. Emerging research has underscored the critical involvement of the gut microbiota and its metabolites, particularly short‑chain fatty acids (SCFAs), in regulating the hepatic immune microenvironment and contributing to the development of HCC. SCFAs play essential roles in the gut‑liver axis by supporting immune homeostasis, modulating lipid metabolism and influencing immune escape mechanisms within the liver. SCFAs are not only products of gut microbiota metabolism but also key regulators of liver metabolism and immune responses. SCFAs play both positive and negative roles in HCC. SCFAs influence T‑cell function and immune responses through the activation of G‑protein‑coupled receptors and the inhibition of histone deacetylases. The present review provided an overview of the current knowledge concerning the regulatory dual effects of SCFAs on the immune microenvironment of HCC, examines their interactions with immune cells via the gut‑liver axis and evaluated their potential as adjuncts in HCC immunotherapy, with the goal of informing future therapeutic strategies.