Open Access

REVIEW

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

Guodong Yu^1,#, Weiying Ge^2,#, Hongliang Yao³, Xuefeng Bai¹, Jianfei Wu¹, Yuan Wang¹, Jiangtao Bai⁴, Yong Cui^1,*, Jijing Han^5,*

1 Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, China
2 Department of Radiology, Affiliated Hospital of Hebei University, Baoding, China
3 The Second Department of general surgery, Hengshui people’s Hospital, Hengshui, China
4 Department of Interventional and Vascular Surgery, Affiliated Hospital of Hebei University, Baoding, China
5 Department of Pediatrics, Affiliated Hospital of Hebei University, Baoding, China

* Corresponding Authors: Yong Cui. Email: ; Jijing Han. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Advancements in Hepatocellular Carcinoma Treatment)

Oncology Research 2026, 34(7), 13 https://doi.org/10.32604/or.2026.080746

Received 13 February 2026; Accepted 31 March 2026; Issue published 16 June 2026

Abstract

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.

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Keywords

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