Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 30:16:1592837.
doi: 10.3389/fimmu.2025.1592837. eCollection 2025.

Metabolic reprogramming in hepatocellular carcinoma: mechanisms of immune evasion and therapeutic implications

Bocheng Gao #  1 , Yan Lu #  1 , Xingyue Lai #  1 , Xi Xu #  1 , Shuhua Gou  1 , Zhida Yang  2 , Yanju Gong  2 , Hong Yang  1
Affiliations
Review

Metabolic reprogramming in hepatocellular carcinoma: mechanisms of immune evasion and therapeutic implications

Bocheng Gao et al. Front Immunol. .

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with limited treatment options for advanced stages. Metabolic reprogramming is a hallmark of cancer, enabling tumor cells to adapt to the harsh tumor microenvironment (TME) and evade immune surveillance. This review involves the role of metabolic reprogramming in HCC, focusing on the dysregulation of glucose, lipid, and amino acid metabolism, and its impact on immune evasion. Key metabolic pathways, such as the Warburg effect, fatty acid synthesis, and glutaminolysis, are discussed, along with their influence on tumor-associated macrophages (TAMs) and immune cell function. Targeting these metabolic alterations presents a promising therapeutic approach to enhance immunotherapy efficacy and improve HCC patient outcomes.

Keywords: TME; hepatocellular carcinoma; immune evasion; immunotherapy; metabolic reprogramming; tumor microenvironment; tumor-associated macrophages (TAMs).

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

    1. Zeng L, Su J, Qiu W, Jin X, Qiu Y, Yu W. Survival outcomes and safety of programmed cell death/programmed cell death ligand 1 inhibitors for unresectable hepatocellular carcinoma: result from phase III trials. Cancer Control. (2022) 29:10732748221092924. doi: 10.1177/10732748221092924 - DOI - PMC - PubMed
    1. Zhai X, Xia Z, Du G, Zhang X, Xia T, Ma D, et al. LRP1B suppresses HCC progression through the NCSTN/PI3K/AKT signaling axis and affects doxorubicin resistance. Genes Dis. (2023) 10:2082–96. doi: 10.1016/j.gendis.2022.10.021 - DOI - PMC - PubMed
    1. Liang R, Hong W, Zhang Y, Ma D, Li J, Shi Y, et al. Deep dissection of stemness-related hierarchies in hepatocellular carcinoma. J Transl Med. (2023) 21:631. doi: 10.1186/s12967-023-04425-8 - DOI - PMC - PubMed
    1. Xia Z, Chen S, He M, Li B, Deng Y, Yi L, et al. Editorial: Targeting metabolism to activate T cells and enhance the efficacy of checkpoint blockade immunotherapy in solid tumors. Front Immunol. (2023) 14:1247178. doi: 10.3389/fimmu.2023.1247178 - DOI - PMC - PubMed
    1. Zhang P, Pei S, Wu L, Xia Z, Wang Q, Huang X, et al. Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma. Front Endocrinol (Lausanne). (2023) 14:1196372. doi: 10.3389/fendo.2023.1196372 - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources