Immunometabolic Reprogramming in Hepatocellular Carcinoma Mechanisms, Biomarkers, and Therapeutic Implications

Hepatocellular carcinoma (HCC) develops in a chronically inflamed and dysregulated liver metabolism, in which tumor progression and resistance to treatment are orchestrated by the changes in cellular metabolism and immune control. Growing evidence recognizes immunometabolic reprogramming as the two-way interaction of metabolic processes and immune cell capabilities as one of the major determinants of immune evasion and heterogeneity of treatment response in HCC. The review aims to comprehensively evaluate immunometabolic reprogramming in hepatocellular carcinoma, with a focus on its role in tumor progression, immune regulation, and its potential for biomarker identification and therapeutic targeting. Dysregulated glycolysis, lipid metabolism, amino acid utilization, and mitochondrial dysfunction contribute to remodeling of the tumor microenvironment and defects in antitumor immunity. Immunometabolic biomarkers derived from tumor tissue, immune cell states, circulating and liquid biopsy platforms, and metabolic imaging are critically examined for their clinical relevance and associations with disease outcomes and treatment responses. Besides, the role of different immunometabolic conditions on therapeutic efficacy, specifically within the frames of immune checkpoint-inhibitor-based and combination regimens, is addressed. Altogether, immunometabolic reprogramming is identified as a common framework of biomarker-based stratification and precision therapeutic techniques in hepatocellular carcinoma.