Lactate and lactylation in hepatocellular carcinoma: A new frontier in metabolic-epigenetic interactions

Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with persistently high and increasing mortality rates. Once regarded merely as a metabolic byproduct, lactate is now recognized as a key metabolite in the tumor microenvironment (TME), where it promotes HCC progression through diverse biological functions. Lactylation, a unique post-translational modification, regulates the TME by altering gene expression via the addition of lactate-derived groups to both histone and non-histone proteins. This review summarizes the role of lactate metabolism in the body, examines its effects on various immune cell populations, and highlights recent advances in anti-HCC therapies targeting lactate.