Cited by 251Cancer, Hypoxia, and MetabolismImmune cells in cancerCancer Immunotherapy and Biomarkers

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Metabolic reprogramming in the tumor microenvironment of liver cancer

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Lin, Jian, Rao, Dongning, Zhang, Mao, Gao, Qiang·2024·Journal of Hematology & Oncology

DOI 10.1186/s13045-024-01527-8PMC PMC10832230

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Abstract

The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements. Overwhelming evidence has illustrated that dysregulated cellular metabolism can, in turn, promote anabolic growth and tumor propagation in a hostile microenvironment. In addition to supporting continuous tumor growth and survival, disrupted metabolic process also creates obstacles for the anticancer immune response and restrains durable clinical remission following immunotherapy. In this review, we elucidate the metabolic communication between liver cancer cells and their surrounding immune cells and discuss how metabolic reprogramming of liver cancer impacts the immune microenvironment and the efficacy of anticancer immunotherapy. We also describe the crucial role of the gut-liver axis in remodeling the metabolic crosstalk of immune surveillance and escape, highlighting novel therapeutic opportunities.

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Fig. 1 Metabolic alterations in PLC. HBV: hepatitis B virus; HCV: hepatitis C virus; MASH: metabolic dysfunction-associated steatohepatitis; MASLD: metabolic dysfunction-associated steatotic liver disease; OE: overexpression; Mut: mutation; PPP: pentose phosphate pathway; HBP: hexosamine biosynthesis pathway; FASN: fatty acid synthase; and SCD: stearoyl-CoA desaturaseCC BY · PubMed Central

Fig. 2 Immune regulation by nutrient competition and oncometabolite production. SAM: S-adenosylmethionine and MTA: 5-methylthioadenosineCC BY · PubMed Central

Fig. 3 Metabolic signaling-mediated immune escape in tumor cells and immune cells. HA: hyaluronan; OSM: oncostatin M; NET: neutrophil extracellular traps; FN1: fibronectin 1; αKG: α-ketoglutarate; and D-2-HG: D-2-hydroxyglutarateCC BY · PubMed Central

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Authors: Lin, J., Rao, D., Zhang, M., & Gao, Q.
Affiliations: Fudan University (CN)
Shanghai Medical College of Fudan University (CN)
Corresponding author: Gao, Qiang
ORCID: Lin, Jian
Rao, Dongning
Zhang, Mao
Gao, Qiang
Venue: Journal of Hematology & Oncology
Publisher: Springer Science and Business Media LLC
Published: 2024-01-31
Volume: 17
Issue: 1
Pages: 6-6
ISSN: 1756-8722 (ISSN-L)
DOI: 10.1186/s13045-024-01527-8
PMC: PMC10832230
OpenAlex: W4391404272
Cited by: 251
References: 231
Citations by year: 2026: 125 · 2025: 110 · 2024: 16
FWCI: 12.25
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: Journal of Hematology & Oncology (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (82103314, 82130077)
Jinshan Hospital Flexible Mobile Talent Research Startup Fund (RXRC-2020-1)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords: metabolic reprogramming, liver cancer, tumor microenvironment, tumor immune microenvironment, cancer immunotherapy, immunotherapy resistance, gut-liver axis, immune surveillance, immune evasion
MeSH terms: Metabolic Reprogramming, Energy Metabolism, Glycolysis, Humans, Immunotherapy, Liver Neoplasms, Neoplasms, Tumor Microenvironment

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Metabolic reprogramming in the tumor microenvironment of liver cancer

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