ArticleCell death and differentiation2025
Spermine synthase engages in macrophages M2 polarization to sabotage antitumor immunity in hepatocellular carcinoma.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota-Associated Kynurenine Accumulation and Macrophage Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell spatial landscape of aggrephagy activity stratifies hepatocellular carcinoma neutrophils and delivers a 5-gene diagnostic panel for patient stratification.Translational oncology · 2026Article
- Injectable multi-component hydrogel as an inhibitor of choline kinase α achieved the treatment of malignant ascites by inhibiting PI3K/AKT/mTOR signaling pathway.Journal of advanced research · 2026Article
- The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Restoration of macrophage mitochondrial dynamics and trafficking with enzymatic magnesium-manganese layered double hydroxide for osteoporotic therapy.Journal of nanobiotechnology · 2026Article
- HKDC1-mediated polyamine rewiring drives lenvatinib resistance and immune escape in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- From guardians to traitors: molecular mechanisms of tumor-induced T cell betrayal.Molecular cancer · 2026Review
- Macrophage-intrinsic and IL-9-dependent arginine metabolism promotes lung tumor growth.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Gut microbial metabolites of amino acids in liver diseases.Gut microbes · 2025Review
- miR-139-5p suppresses hepatocellular carcinoma progression by targeting SMOX to inhibit AKT-mTOR pathway and epithelial-mesenchymal transition.Scientific reports · 2025Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Total favonoids of Desmodium Styracifolium relieve renal ischemia-reperfusion injury by suppressing ferroptosis through P53/SLC7A11/GPX4 signaling pathway.Journal of bioenergetics and biomembranes · 2025Article
- Important Role of Bacterial Metabolites in Development and Adjuvant Therapy for Hepatocellular Carcinoma.Current oncology (Toronto, Ont.) · 2025Review
- Gut microbiota L-ornithine promotes resistance to obesity through metabolites mediated immunosuppressive macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Spermine synthase in Snyder-Robinson syndrome and cancer.Molecular biology reports · 2025Review
- The arginine metabolism battlefield: how metabolite exchange in the tumor microenvironment shapes an immunosuppressive ecosystem.Cancer biology & medicine · 2025Article
- Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025Review
- Spermine accumulation via spermine synthase promotes tumor cell proliferation in head and neck squamous cell carcinoma.BMC cancer · 2025Article
- Malignant epithelia cells-derived spermine induces APOE+ macrophages to suppress tumor immunity in adenocarcinoma of the esophagogastric junction.Frontiers in medicine · 2025Article
- Cyclophilin J Reprograms Tumor-associated Macrophages to Exert an Anti-tumor Effect in Liver Cancer.International journal of biological sciences · 2025Article
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Authors and funding
11 authors.
Funding
Abstract
Disturbances in tumor cell metabolism reshape the tumor microenvironment (TME) and impair antitumor immunity, but the implicit mechanisms remain elusive. Here, we found that spermine synthase (SMS) was significantly upregulated in tumor cells, which correlated positively with the immunosuppressive microenvironment and predicted poor survival in hepatocellular carcinoma (HCC) patients. Via "subcutaneous" and "orthotopic" HCC syngeneic mouse models and a series of in vitro coculture experiments, we identified elevated SMS levels in HCC cells played a role in immune escape mainly through its metabolic product spermine, which induced M2 polarization of tumor-associated macrophages (TAMs) and subsequently corresponded with a decreased antitumor functionality of CD8
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