Academic Journal
ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis Through Symbiotic Adhesion and Reverse Migration.
| Τίτλος: | ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis Through Symbiotic Adhesion and Reverse Migration. |
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| Συγγραφείς: | Wu L; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Xu Z; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Wang J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas., Liu F; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Ding Y; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Gao Y; Department of Cancer Biology and Genetics, The Ohio State University College of Medicine, Columbus, Ohio.; The Ohio State University Comprehensive Cancer Center, Columbus, Ohio., Wang S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, Texas., Liu J; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Chan HL; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, Texas.; Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas.; The Robert and Janice McNair Foundation MD/PhD Scholars, Baylor College of Medicine, Houston, Texas., Wu W; Advanced Technology Cores, Baylor College of Medicine, Houston, Texas., Wu YH; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Yu L; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Hao X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Li X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Edwards DG; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Sha C; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, Texas.; Medical Scientist Training Program, Baylor College of Medicine, Houston, Texas., Lee TD; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Quantitative and Computational Biosciences Graduate Program, Baylor College of Medicine, Houston, Texas., Guan N; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Aguirre S; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Becerra-Dominguez L; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, Texas., Hoffman D; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Chen X; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Rivas CH; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, Texas., Yan XG; The Awty International School, Houston, Texas., Bado IL; Icahn School of Medicine at Mount Sinai , New York, New York.; Mount Sinai Tisch Cancer Center, New York, New York.; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York., Zhang W; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas., Zhu Q; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas.; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Sreekumar A; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas., Satcher RL; Department of Orthopedic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Zhang XH; Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas. |
| Πηγή: | Cancer research [Cancer Res] 2026 Aug 14; Vol. 86 (16), pp. 4007-4027. |
| Τύπος έκδοσης: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE |
| Imprint Name(s): | Publication: Baltimore, Md. : American Association for Cancer Research Original Publication: Chicago [etc.] |
| Ιατρικοί όροι (MeSH): | Neutrophils*/metabolism , Neutrophils*/immunology , Neutrophils*/pathology , Intercellular Adhesion Molecule-1*/metabolism , Intercellular Adhesion Molecule-1*/genetics , Triple Negative Breast Neoplasms*/pathology , Triple Negative Breast Neoplasms*/immunology , Triple Negative Breast Neoplasms*/metabolism , Triple Negative Breast Neoplasms*/genetics, Tumor Microenvironment/immunology ; Humans ; Animals ; Cell Adhesion ; Female ; Cell Movement ; Mice ; Neoplasm Metastasis ; Cell Line, Tumor |
| Περίληψη: | Neutrophils are a prominent component of the tumor microenvironment (TME) that can have both pro- and antitumor functions. By analyzing neutrophils across different human cancers, we revealed an ICAM1high subset enriched in the TME, which was also observed in murine triple-negative breast cancer (TNBC) models. ICAM1high neutrophils exhibited an enhanced capacity for cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion conferred mutual advantages to both cell types. In contrast, cancer cells with mesenchymal-like phenotypes were vulnerable to neutrophil-mediated cytotoxicity due to decreased cell adhesion and elastase resistance. These opposite effects drove tumor evolution toward a dichotomy of neutrophil-enriched, epithelial-like ecosystems and macrophage-enriched, mesenchymal-like ecosystems. As ICAM1high neutrophils can reverse migrate from tissue into the circulation, the adhesive and reverse migratory properties together mediate metastatic intravasation. Spatial transcriptomic and tissue microarray analyses demonstrated interactions between tumor cells, neutrophils, and endothelial cells in human TNBC, particularly in non-Hispanic Europeans compared with African American patients. Together, this study demonstrated tumor-immune coevolution in which neutrophils instruct the phenotypes and metastatic behaviors of TNBC, which may preferentially occur in patients of certain ancestries. Significance: A distinct subset of ICAMhigh tumor-infiltrating neutrophils with increased adhesion and reverse transendothelial migration shapes tumor phenotypes and metastatic potential through mutually beneficial interactions with epithelial cancer cells. (©2026 American Association for Cancer Research.) |
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| Grant Information: | R01 CA277838 United States CA NCI NIH HHS; R00 CA279899 United States CA NCI NIH HHS; HT9425-23-1-0493 U.S. Department of Defense (DOD); P30EY002520 National Institutes of Health (NIH); CA227904 National Cancer Institute (NCI); P50CA186784 National Cancer Institute (NCI); S10 OD023469 United States OD NIH HHS; S10OD025240 National Institutes of Health (NIH); RP200504 Cancer Prevention and Research Institute of Texas (CPRIT); S10 RR024574 United States RR NCRR NIH HHS; S10OD032185 National Institutes of Health (NIH); S10OD023469 National Institutes of Health (NIH); CA251950 National Cancer Institute (NCI); R01 CA271498 United States CA NCI NIH HHS; S10 OD032185 United States OD NIH HHS; CA221946 National Cancer Institute (NCI); S10 OD025240 United States OD NIH HHS; P30 CA125123 United States CA NCI NIH HHS; R01 CA221946 United States CA NCI NIH HHS; RP180672 Cancer Prevention and Research Institute of Texas (CPRIT); CA253533 National Cancer Institute (NCI); CA183878 National Cancer Institute (NCI); P30 EY002520 United States EY NEI NIH HHS; R01 CA251950 United States CA NCI NIH HHS; R01 CA183878 United States CA NCI NIH HHS; K99 CA279899 United States CA NCI NIH HHS; R01 CA227904 United States CA NCI NIH HHS; CA125123 National Institutes of Health (NIH); P50 CA186784 United States CA NCI NIH HHS |
| Molecular Sequence: | GEO GSE284278; GSE284277; GSE319442; GSE284279; GSE301336; GSE301335 |
| Substance Nomenclature: | 126547-89-5 (Intercellular Adhesion Molecule-1) 0 (ICAM1 protein, human) |
| Entry Date(s): | Date Created: 20260528 Date Completed: 20260814 Latest Revision: 20260922 |
| Update Code: | 20260922 |
| PubMed Central ID: | PMC13293467 |
| DOI: | 10.1158/0008-5472.CAN-25-3935 |
| PMID: | 42207963 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1538-7445 |
|---|---|
| DOI: | 10.1158/0008-5472.CAN-25-3935 |