Academic Journal
Single-cell transcriptomic unveils tumor-mediated reprogramming of neutrophils and their unique vulnerability that inhibits metastasis.
| Τίτλος: | Single-cell transcriptomic unveils tumor-mediated reprogramming of neutrophils and their unique vulnerability that inhibits metastasis. |
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| Συγγραφείς: | Putzbach W; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Zappia MP; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Magdy A; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Li J; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Nogueira V; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Lou K; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA., Shokat KM; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA., Islam ABMMK; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Frolov M; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA., Hay N; Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA.; Research and Development Section, Jesse Brown VA Medical Center, Chicago, IL 60612, USA.; University of Illinois Cancer Center, University of Illinois at Chicago, Chicago, IL 60612, USA. |
| Πηγή: | Science advances [Sci Adv] 2026 Jul 17; Vol. 12 (29), pp. eaee9308. Date of Electronic Publication: 2026 Jul 15. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]- |
| Ιατρικοί όροι (MeSH): | Neutrophils*/metabolism , Neutrophils*/pathology , Neutrophils*/drug effects , Cellular Reprogramming*/genetics , Transcriptome*, Tumor Microenvironment/genetics ; Animals ; Mice ; Neoplasm Metastasis ; Single-Cell Gene Expression Analysis ; Single-Cell Analysis ; Female ; Gene Expression Regulation, Neoplastic ; Granulocyte Colony-Stimulating Factor |
| Περίληψη: | Neutrophils are protumorigenic and prometastatic in tumor-bearing mice. Comprehensive single-cell RNA sequencing analyses on various tissues of naïve and tumor-bearing MMTV-PyMT (mouse mammary tumor virus-polyoma middle T antigen) mice unraveled a neutrophil reprogramming process and uncovered a strategy to selectively target reprogrammed neutrophils. Transcriptional reprogramming of neutrophils in tumor-bearing mice is initiated in the bone marrow (BM) by granulocyte colony-stimulating factor (G-CSF). Among the seven neutrophil clusters in the BM, the abundance of one cluster is markedly increased whereas another cluster is diminished in tumor-bearing mice. This reprogramming endures across tissue types including blood, tumor microenvironment, and the metastatic niche in the lungs. Thus, in all tissues tested, neutrophils derived from tumor-bearing mice are transcriptionally distinct from those derived from naïve mice. Among the genes that are markedly induced are members of the Ifitm family. We leverage this facet to selectively target reprogrammed neutrophils through treatment with Rapalink-1-an mTOR (mechanistic target of rapamycin) inhibitor-whose intake is greatly enhanced by IFITM proteins. Reprogrammed neutrophils selectively uptake Rapalink-1, which selectively eradicate them in vivo and normalized the neutrophil-to-lymphocyte ratio in tumor-bearing mice without affecting naïve neutrophils. Last, Rapalink-1 inhibited metastasis of a Rapalink-1-resistant tumor. Thus, Rapalink-1 not only could affect the primary tumor but also selectively eliminates tumor-reprogrammed neutrophils to diminish metastasis. |
| Substance Nomenclature: | 143011-72-7 (Granulocyte Colony-Stimulating Factor) |
| Entry Date(s): | Date Created: 20260715 Date Completed: 20260715 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13371899 |
| DOI: | 10.1126/sciadv.aee9308 |
| PMID: | 42455928 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2375-2548 |
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| DOI: | 10.1126/sciadv.aee9308 |