ArticleCellular & molecular immunology2025
IL33-induced lipid droplet formation in mature low-density neutrophils drives colorectal cancer liver metastasis.
Article in Cellular & molecular immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Neutrophil-based immunotherapy: A metabolic lens on mechanisms and therapeutic implications.Clinical and translational medicine · 2026Review
- Fatty Acid Metabolism and Hypoxia in the Tumor Microenvironment: Metabolic Adaptation and Clinical Potential in Colorectal Cancer.Biomedicines · 2026Review
- Neutrophil extracellular traps in colorectal cancer: context-dependent roles from inflammatory carcinogenesis to liver metastasis and therapeutic targeting.Journal of translational medicine · 2026Review
- Roles of Lcn2 and neuroinflammation in a scopolamine-induced cognitive impairment animal model: implication of the NLRP3 inflammasome pathway.Genes & genomics · 2026Article
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Spatial immune niche remodeling of the neutrophil-macrophage axis inchronic liver disease.Frontiers in cell and developmental biology · 2026Review
- Colorectal cancer liver metastases: mechanism and therapy.Frontiers in immunology · 2026Review
- Advances in the study of low-density neutrophils in rheumatic diseases.Frontiers in immunology · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Pyroptosis in Alzheimer's Disease: Mechanisms and Therapeutic Potential.Cellular and molecular neurobiology · 2025Review
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Authors and funding
13 authors.
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Abstract
The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells. It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs. Here, we demonstrate that mature low-density neutrophils in colorectal cancer patients abnormally accumulate neutral lipids and induce the reactivation of dormant tumor cells, a process regulated by hepatic stellate cells. Mechanistically, activated hepatic stellate cells increased DGAT1/2-dependent lipid droplet synthesis in low-density neutrophils through the secretion of IL33, thereby maintaining the survival and immunosuppressive function of these neutrophils. The uptake of lipids from lipid-laden low-density neutrophils drives dormant tumor cell reactivation through the potentiation of β-oxidation and the stimulation of protumorigenic eicosanoid synthesis. In mouse models, targeting IL33 blocked neutrophil lipid synthesis, decreased the colonization of colorectal cancer cells in the liver, and enhanced the efficacy of immunotherapy. Overall, our study revealed that lipid accumulation in mature low-density neutrophils regulates the growth of dormant tumor cells and antitumor immunity to facilitate colorectal cancer liver metastasis. Targeting IL33 could be a promising therapeutic approach for colorectal cancer liver metastases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.