ArticleCancer research2023
Polyunsaturated Fatty Acid-Bound α-Fetoprotein Promotes Immune Suppression by Altering Human Dendritic Cell Metabolism.
Article in Cancer research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- A sequentially activated afterglow probe for AND-gated imaging of alpha-fetoprotein in hepatocellular carcinoma.Bioactive materials · 2027Article
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Lipid metabolism in homeostasis and disease.Signal transduction and targeted therapy · 2026Review
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Glycolysis in the tumor microenvironment shapes dendritic cell function and antitumor immunity.Frontiers in immunology · 2026Review
- Dietary Polyunsaturated Fatty Acids Regulate Dendritic Cell Function via Nrf2-dependent Control of Ferroptosis.Research square · 2025Article
- Decoding immunometabolism with next-generation tools: lessons from dendritic cells and T cells.The EMBO journal · 2025Review
- Spatial Immunometabolism: Integrating Technologies to Decode Cellular Metabolism in Tissues.European journal of immunology · 2025Review
- Exploring the Multifunctional Role of Alpha-Fetoprotein in Cancer Progression: Implications for Targeted Therapy in Hepatocellular Carcinoma and Beyond.International journal of molecular sciences · 2025Review
- MCT1 lactate transporter blockade re-invigorates anti-tumor immunity through metabolic rewiring of dendritic cells in melanoma.Nature communications · 2025Article
- Comparison of Alpha-fetoprotein-positive and AFP-negative patients with advanced gastroesophageal junction or gastric cancer receiving immunotherapy: an analysis stratified by HER2 status.American journal of cancer research · 2025Article
- Enhancing survival outcomes in unresectable hepatocellular carcinoma: a prospective cohort study on the effects of Huaier granules with targeted therapy plus immunotherapy.Frontiers in pharmacology · 2025Article
- Fatty acid metabolism: A new target for nasopharyngeal carcinoma therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Analysis of Immunosuppression and Antioxidant Damage in Diploid and Triploid Crucian Carp (Metabolites · 2024Article
- Nomogram-based prognostic stratification for patients with large hepatocellular carcinoma: a population study of SEER database and a Chinese cohort.Journal of gastrointestinal oncology · 2024Article
- Long-chain acyl-CoA synthetase 4-mediated mitochondrial fatty acid metabolism and dendritic cell antigen presentation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Structural characteristics of alpha-fetoprotein, including N-glycosylation, metal ion and fatty acid binding sites.Communications biology · 2024Article
- Immune Assessment Today: Optimizing and Standardizing Efforts to Monitor Immune Responses in Cancer and Beyond.Cancers · 2024Article
- Unlocking Dendritic Cell-Based Vaccine Efficacy through Genetic Modulation-How Soon Is Now?Genes · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
α-Fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell (DC) differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human DC functional suppression, here, we used two recently described single-cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of DCs were significantly increased by tumor-derived, but not normal cord blood-derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on DC stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids (PUFA) than cord blood-derived AFP. PUFAs bound to AFP increased metabolic skewing and promoted DC functional suppression. PUFAs inhibited DC differentiation in vitro, and ω-6 PUFAs conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit antitumor immunity. SIGNIFICANCE: α-Fetoprotein (AFP) is a secreted tumor protein and biomarker with impact on immunity. Fatty acid-bound AFP promotes immune suppression by skewing human dendritic cell metabolism toward glycolysis and reduced immune stimulation.
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