{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:49:59Z","timestamp":1790628599200,"version":"4.1.0"},"reference-count":79,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":30,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-026-76459-7","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T17:34:06Z","timestamp":1786469646000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neutrophil extracellular traps promote liver metastasis by impairing NK cell-dependent tumor surveillance via CCDC25"],"prefix":"10.1038","volume":"17","author":[{"given":"Yetong","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heliang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3314-8543","authenticated-orcid":false,"given":"Yujiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghua","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyue","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0409-6900","authenticated-orcid":false,"given":"Xiaoming","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linxi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieyu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-9049","authenticated-orcid":false,"given":"Erwei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6326-5231","authenticated-orcid":false,"given":"Linbin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"76459_CR1","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41591-020-1131-x","volume":"27","author":"J Yu","year":"2021","unstructured":"Yu, J. et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nat. Med. 27, 152\u2013164 (2021).","journal-title":"Nat. Med."},{"key":"76459_CR2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41572-021-00261-6","volume":"7","author":"DI Tsilimigras","year":"2021","unstructured":"Tsilimigras, D. I. et al. Liver metastases. Nat. Rev. Dis. Primers 7, 27 (2021).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"76459_CR3","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1038\/s43018-023-00595-y","volume":"4","author":"A P\u00e9rez-Gonz\u00e1lez","year":"2023","unstructured":"P\u00e9rez-Gonz\u00e1lez, A., B\u00e9vant, K. & Blanpain, C. Cancer cell plasticity during tumor progression, metastasis and response to therapy. Nat Cancer 4, 1063\u20131082 (2023).","journal-title":"Nat Cancer"},{"key":"76459_CR4","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s41586-021-03614-z","volume":"594","author":"AL Correia","year":"2021","unstructured":"Correia, A. L. et al. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy. Nature 594, 566\u2013571 (2021).","journal-title":"Nature"},{"key":"76459_CR5","doi-asserted-by":"crossref","unstructured":"Costa-Silva, B. et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 17, 816\u2013826 (2015).","DOI":"10.1038\/ncb3169"},{"key":"76459_CR6","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.ccell.2016.09.011","volume":"30","author":"Y Liu","year":"2016","unstructured":"Liu, Y. & Cao, X. Characteristics and significance of the Pre-metastatic Niche. Cancer Cell 30, 668\u2013681 (2016).","journal-title":"Cancer Cell"},{"key":"76459_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00888-7","author":"MH Shahzad","year":"2025","unstructured":"Shahzad, M. H., Rayes, R. F., Cools-Lartigue, J. & Spicer, J. D. Neutrophil extracellular traps in cancer. Nat Rev Cancer https:\/\/doi.org\/10.1038\/s41568-025-00888-7 (2025).","journal-title":"Nat Rev Cancer"},{"key":"76459_CR8","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/s43018-021-00194-9","volume":"2","author":"SAC McDowell","year":"2021","unstructured":"McDowell, S. A. C. et al. Neutrophil oxidative stress mediates obesity-associated vascular dysfunction and metastatic transmigration. Nat Cancer 2, 545\u2013562 (2021).","journal-title":"Nat Cancer"},{"key":"76459_CR9","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/s41586-020-2394-6","volume":"583","author":"L Yang","year":"2020","unstructured":"Yang, L. et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature 583, 133\u2013138 (2020).","journal-title":"Nature"},{"key":"76459_CR10","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1172\/JCI67484","volume":"123","author":"J Cools-Lartigue","year":"2013","unstructured":"Cools-Lartigue, J. et al. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Invest 123, 3446\u20133458 (2013).","journal-title":"J. Clin. Invest"},{"key":"76459_CR11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao4227","volume":"361","author":"J Albrengues","year":"2018","unstructured":"Albrengues, J. et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361, eaao4227 (2018).","journal-title":"Science"},{"key":"76459_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09278-3","author":"JM Adrover","year":"2025","unstructured":"Adrover, J. M. et al. Neutrophils drive vascular occlusion, tumour necrosis and metastasis. Nature https:\/\/doi.org\/10.1038\/s41586-025-09278-3 (2025).","journal-title":"Nature"},{"key":"76459_CR13","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/j.immuni.2020.03.001","volume":"52","author":"\u00c1. Teijeira","year":"2020","unstructured":"Teijeira, \u00c1. et al. CXCR1 and CXCR2 Chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with Immune Cytotoxicity. Immunity 52, 856\u2013871.e8 (2020).","journal-title":"Immunity"},{"key":"76459_CR14","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ccell.2024.12.004","volume":"43","author":"W Lee","year":"2025","unstructured":"Lee, W. et al. Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10. Cancer Cell 43, 69\u201385.e11 (2025).","journal-title":"Cancer Cell"},{"key":"76459_CR15","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.1038\/s41591-024-03075-7","volume":"30","author":"L Bojmar","year":"2024","unstructured":"Bojmar, L. et al. Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. Nat. Med. 30, 2170\u20132180 (2024).","journal-title":"Nat. Med."},{"key":"76459_CR16","doi-asserted-by":"publisher","unstructured":"Liu, K. et al. 5-HT orchestrates histone serotonylation and citrullination to drive neutrophil extracellular traps and liver metastasis. J. Clin. Invest. 135, https:\/\/doi.org\/10.1172\/jci183544 (2025).","DOI":"10.1172\/jci183544"},{"key":"76459_CR17","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aax7942","volume":"14","author":"F Apel","year":"2021","unstructured":"Apel, F. et al. The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps. Sci. Signal. 14, eaax7942 (2021).","journal-title":"Sci. Signal."},{"key":"76459_CR18","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41392-024-01881-6","volume":"9","author":"J Chen","year":"2024","unstructured":"Chen, J. et al. DNA of neutrophil extracellular traps promote NF-\u03baB-dependent autoimmunity via cGAS\/TLR9 in chronic obstructive pulmonary disease. Sig. Transduct. Target. Ther. 9, 163 (2024).","journal-title":"Sig. Transduct. Target. Ther."},{"key":"76459_CR19","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01286-7","author":"S Wang","year":"2025","unstructured":"Wang, S. et al. The NET-DNA-CCDC25 inhibitor di-Pal-MTO suppresses tumor progression and promotes the innate immune response. Cell Mol. Immunol. https:\/\/doi.org\/10.1038\/s41423-025-01286-7 (2025).","journal-title":"Cell Mol. Immunol."},{"key":"76459_CR20","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1038\/s41388-024-03114-0","volume":"43","author":"X Tang","year":"2024","unstructured":"Tang, X. et al. Single-cell profiling reveals altered immune landscape and impaired NK cell function in gastric cancer liver metastasis. Oncogene 43, 2635\u20132646 (2024).","journal-title":"Oncogene"},{"key":"76459_CR21","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/s41392-024-01933-x","volume":"9","author":"H Wang","year":"2024","unstructured":"Wang, H. et al. Neutrophil extracellular traps in homeostasis and disease. Sig. Transduct. Target. Ther. 9, 235 (2024).","journal-title":"Sig. Transduct. Target. Ther."},{"key":"76459_CR22","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1038\/s41423-020-0412-0","volume":"17","author":"M Metzemaekers","year":"2020","unstructured":"Metzemaekers, M., Gouwy, M. & Proost, P. Neutrophil chemoattractant receptors in health and disease: double-edged swords. Cell Mol. Immunol. 17, 433\u2013450 (2020).","journal-title":"Cell Mol. Immunol."},{"key":"76459_CR23","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.molmed.2023.09.003","volume":"30","author":"G Lazennec","year":"2024","unstructured":"Lazennec, G., Rajarathnam, K. & Richmond, A. CXCR2 chemokine receptor \u2013 a master regulator in cancer and physiology. Trends Mol. Med. 30, 37\u201355 (2024).","journal-title":"Trends Mol. Med."},{"key":"76459_CR24","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1038\/sj.bjc.6605055","volume":"100","author":"S Singh","year":"2009","unstructured":"Singh, S., Nannuru, K. C., Sadanandam, A., Varney, M. L. & Singh, R. K. CXCR1 and CXCR2 enhances human melanoma tumourigenesis, growth and invasion. Br. J. Cancer 100, 1638\u20131646 (2009).","journal-title":"Br. J. Cancer"},{"key":"76459_CR25","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1158\/0008-5472.CAN-12-0263","volume":"73","author":"P Saintigny","year":"2013","unstructured":"Saintigny, P. et al. CXCR2 Expression in tumor cells is a poor prognostic factor and promotes invasion and metastasis in lung adenocarcinoma. Cancer Res. 73, 571\u2013582 (2013).","journal-title":"Cancer Res."},{"key":"76459_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41771-z","volume":"14","author":"SK Thomas","year":"2023","unstructured":"Thomas, S. K. et al. Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice. Nat. Commun. 14, 6330 (2023).","journal-title":"Nat. Commun."},{"key":"76459_CR27","doi-asserted-by":"publisher","unstructured":"Daemen, S., Chan, M. M. & Schilling, J. D. Comprehensive analysis of liver macrophage composition by flow cytometry and immunofluorescence in murine NASH. STAR Protoc. 2, https:\/\/doi.org\/10.1016\/j.xpro.2021.100511 (2021).","DOI":"10.1016\/j.xpro.2021.100511"},{"key":"76459_CR28","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1002\/hep.22034","volume":"47","author":"B Gao","year":"2008","unstructured":"Gao, B., Jeong, W.-I. & Tian, Z. Liver: An organ with predominant innate immunity. Hepatology 47, 729\u2013736 (2008).","journal-title":"Hepatology"},{"key":"76459_CR29","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/s41423-018-0024-0","volume":"16","author":"CM de Bont","year":"2019","unstructured":"de Bont, C. M., Boelens, W. C. & Pruijn, G. J. M. NETosis, complement, and coagulation: a triangular relationship. Cell Mol. Immunol. 16, 19\u201327 (2019).","journal-title":"Cell Mol. Immunol."},{"key":"76459_CR30","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/nri.2017.97","volume":"18","author":"ES Reis","year":"2018","unstructured":"Reis, E. S., Mastellos, D. C., Ricklin, D., Mantovani, A. & Lambris, J. D. Complement in cancer: untangling an intricate relationship. Nat. Rev. Immunol. 18, 5\u201318 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"76459_CR31","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/ncb2000","volume":"12","author":"M Ostrowski","year":"2010","unstructured":"Ostrowski, M. et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19\u201330 (2010).","journal-title":"Nat. Cell Biol."},{"key":"76459_CR32","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1038\/nature16985","volume":"531","author":"MB Headley","year":"2016","unstructured":"Headley, M. B. et al. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature 531, 513\u2013517 (2016).","journal-title":"Nature"},{"key":"76459_CR33","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1007\/s10555-021-09998-8","volume":"40","author":"VM Haak","year":"2021","unstructured":"Haak, V. M., Huang, S. & Panigrahy, D. Debris-stimulated tumor growth: a Pandora\u2019s box? Cancer Metastasis Rev. 40, 791\u2013801 (2021).","journal-title":"Cancer Metastasis Rev."},{"key":"76459_CR34","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","volume":"24","author":"M Binnewies","year":"2018","unstructured":"Binnewies, M. et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 24, 541\u2013550 (2018).","journal-title":"Nat. Med."},{"key":"76459_CR35","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1016\/j.cell.2023.02.020","volume":"186","author":"DJ Kloosterman","year":"2023","unstructured":"Kloosterman, D. J. & Akkari, L. Macrophages at the interface of the co-evolving cancer ecosystem. Cell 186, 1627\u20131651 (2023).","journal-title":"Cell"},{"key":"76459_CR36","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/0092-8674(80)90619-4","volume":"20","author":"S MacLean-Fletcher","year":"1980","unstructured":"MacLean-Fletcher, S. & Pollard, T. D. Mechanism of action of cytochalasin B on actin. Cell 20, 329\u2013341 (1980).","journal-title":"Cell"},{"key":"76459_CR37","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.2c11280","author":"H Liang","year":"2023","unstructured":"Liang, H. et al. Nanoparticulate Cationic Poly(amino acid)s Block Cancer Metastases by Destructing Neutrophil Extracellular Traps. ACS Nano https:\/\/doi.org\/10.1021\/acsnano.2c11280 (2023).","journal-title":"ACS Nano"},{"key":"76459_CR38","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-22410-x","volume":"12","author":"Q Tang","year":"2022","unstructured":"Tang, Q. et al. Enhanced CHOLESTEROL biosynthesis promotes breast cancer metastasis via modulating CCDC25 expression and neutrophil extracellular traps formation. Sci. Rep. 12, 17350 (2022).","journal-title":"Sci. Rep."},{"key":"76459_CR39","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1084\/jem.20100239","volume":"207","author":"P Li","year":"2010","unstructured":"Li, P. et al. PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps. J. Exp. Med. 207, 1853\u20131862 (2010).","journal-title":"J. Exp. Med."},{"key":"76459_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-00988-1","author":"M Nie","year":"2025","unstructured":"Nie, M. et al. Cardiomyocyte-localized CCDC25 senses NET DNA to promote doxorubicin cardiotoxicity by activating autophagic flux. Nat. Cancer https:\/\/doi.org\/10.1038\/s43018-025-00988-1 (2025).","journal-title":"Nat. Cancer"},{"key":"76459_CR41","first-page":"3808","volume":"54","author":"S Yasumura","year":"1994","unstructured":"Yasumura, S. et al. Immunotherapy of liver metastases of human gastric carcinoma with interleukin 2-activated natural killer cells. Cancer Res. 54, 3808\u20133816 (1994).","journal-title":"Cancer Res."},{"key":"76459_CR42","first-page":"1599","volume":"56","author":"K Okada","year":"1996","unstructured":"Okada, K. et al. Elimination of established liver metastases by human interleukin 2-activated natural killer cells after locoregional or systemic adoptive transfer1. Cancer Res. 56, 1599\u20131608 (1996).","journal-title":"Cancer Res."},{"key":"76459_CR43","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ccell.2017.06.009","volume":"32","author":"A L\u00f3pez-Soto","year":"2017","unstructured":"L\u00f3pez-Soto, A., Gonzalez, S., Smyth, M. J. & Galluzzi, L. Control of metastasis by NK cells. Cancer Cell 32, 135\u2013154 (2017).","journal-title":"Cancer Cell"},{"key":"76459_CR44","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nrc.2015.5","volume":"16","author":"MG Morvan","year":"2016","unstructured":"Morvan, M. G. & Lanier, L. L. NK cells and cancer: you can teach innate cells new tricks. Nat. Rev. Cancer 16, 7\u201319 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"76459_CR45","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1038\/nm1325","volume":"11","author":"M Kortylewski","year":"2005","unstructured":"Kortylewski, M. et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 11, 1314\u20131321 (2005).","journal-title":"Nat. Med."},{"key":"76459_CR46","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nri1995","volume":"7","author":"H Yu","year":"2007","unstructured":"Yu, H., Kortylewski, M. & Pardoll, D. Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat. Rev. Immunol. 7, 41\u201351 (2007).","journal-title":"Nat. Rev. Immunol."},{"key":"76459_CR47","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1182\/blood-2014-03-564450","volume":"124","author":"D Gotthardt","year":"2014","unstructured":"Gotthardt, D. et al. Loss of STAT3 in murine NK cells enhances NK cell\u2013dependent tumor surveillance. Blood 124, 2370\u20132379 (2014).","journal-title":"Blood"},{"key":"76459_CR48","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1126\/science.aaz4165","volume":"368","author":"C Weber","year":"2020","unstructured":"Weber, C. et al. Temperature-dependent sex determination is mediated by pSTAT3 repression of Kdm6b. Science 368, 303\u2013306 (2020).","journal-title":"Science"},{"key":"76459_CR49","doi-asserted-by":"publisher","first-page":"3197","DOI":"10.1016\/j.devcel.2024.09.003","volume":"59","author":"AEP Loftus","year":"2024","unstructured":"Loftus, A. E. P. et al. An ILK\/STAT3 pathway controls glioblastoma stem cell plasticity. Dev. Cell 59, 3197\u20133212 (2024).","journal-title":"Dev. Cell"},{"key":"76459_CR50","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.stem.2020.04.005","volume":"27","author":"K Rothe","year":"2020","unstructured":"Rothe, K. et al. Integrin-linked kinase mediates therapeutic resistance of quiescent CML stem cells to tyrosine kinase inhibitors. Cell Stem Cell 27, 110\u2013124 (2020).","journal-title":"Cell Stem Cell"},{"key":"76459_CR51","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1158\/0008-5472.CAN-06-3166","volume":"67","author":"Y Tabe","year":"2007","unstructured":"Tabe, Y. et al. Activation of integrin-linked kinase is a critical prosurvival pathway induced in leukemic cells by bone marrow\u2013derived stromal cells. Cancer Res. 67, 684\u2013694 (2007).","journal-title":"Cancer Res."},{"key":"76459_CR52","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1158\/0008-5472.CAN-04-2940","volume":"65","author":"CYF Yau","year":"2005","unstructured":"Yau, C. Y. F., Wheeler, J. J., Sutton, K. L. & Hedley, D. W. Inhibition of integrin-linked kinase by a selective small molecule inhibitor, QLT0254, inhibits the PI3K\/PKB\/mTOR, Stat3, and FKHR pathways and tumor growth, and enhances gemcitabine-induced apoptosis in human orthotopic primary pancreatic cancer xenografts. Cancer Res. 65, 1497\u20131504 (2005).","journal-title":"Cancer Res."},{"key":"76459_CR53","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1007\/s10555-024-10198-3","volume":"43","author":"Y Qiu","year":"2024","unstructured":"Qiu, Y., Gao, T. & Smith, B. R. Mechanical deformation and death of circulating tumor cells in the bloodstream. Cancer Metastasis Rev. 43, 1489\u20131510 (2024).","journal-title":"Cancer Metastasis Rev."},{"key":"76459_CR54","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1038\/430973a","volume":"430","author":"LA Liotta","year":"2004","unstructured":"Liotta, L. A. & Kohn, E. Cancer and the homeless cell. Nature 430, 973\u2013974 (2004).","journal-title":"Nature"},{"key":"76459_CR55","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/j.ccell.2025.02.017","volume":"43","author":"S Lamorte","year":"2025","unstructured":"Lamorte, S. et al. Lymph node macrophages drive immune tolerance and resistance to cancer therapy by induction of the immune-regulatory cytokine IL-33. Cancer Cell 43, 955\u2013969 (2025).","journal-title":"Cancer Cell"},{"key":"76459_CR56","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1038\/s43018-024-00731-2","volume":"5","author":"Y Astuti","year":"2024","unstructured":"Astuti, Y. et al. Efferocytosis reprograms the tumor microenvironment to promote pancreatic cancer liver metastasis. Nat. Cancer 5, 774\u2013790 (2024).","journal-title":"Nat. Cancer"},{"key":"76459_CR57","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41573-023-00846-8","volume":"23","author":"YR Miao","year":"2024","unstructured":"Miao, Y. R., Rankin, E. B. & Giaccia, A. J. Therapeutic targeting of the functionally elusive TAM receptor family. Nat. Rev. Drug Discov. 23, 201\u2013217 (2024).","journal-title":"Nat. Rev. Drug Discov."},{"key":"76459_CR58","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1038\/cmi.2016.3","volume":"13","author":"MW Robinson","year":"2016","unstructured":"Robinson, M. W., Harmon, C. & O\u2019Farrelly, C. Liver immunology and its role in inflammation and homeostasis. Cell Mol. Immunol. 13, 267\u2013276 (2016).","journal-title":"Cell Mol. Immunol."},{"key":"76459_CR59","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/S0140-6736(23)01524-6","volume":"403","author":"EE West","year":"2024","unstructured":"West, E. E., Woodruff, T., Fremeaux-Bacchi, V. & Kemper, C. Complement in human disease: approved and up-and-coming therapeutics. Lancet 403, 392\u2013405 (2024).","journal-title":"Lancet"},{"key":"76459_CR60","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1056\/NEJMoa2410316","volume":"392","author":"V Perkovic","year":"2025","unstructured":"Perkovic, V. et al. Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy. N. Engl. J. Med. 392, 531\u2013543 (2025).","journal-title":"N. Engl. J. Med."},{"key":"76459_CR61","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1158\/0008-5472.CAN-23-2986","volume":"84","author":"M Song","year":"2024","unstructured":"Song, M. et al. DNA of Neutrophil extracellular traps binds TMCO6 to impair CD8+ T-cell immunity in hepatocellular carcinoma. Cancer Res. 84, 1613\u20131629 (2024).","journal-title":"Cancer Res."},{"key":"76459_CR62","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.immuni.2021.04.019","volume":"54","author":"\u00c1 de Mingo Pulido","year":"2021","unstructured":"de Mingo Pulido, \u00c1 et al. The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. Immunity 54, 1154\u20131167 (2021).","journal-title":"Immunity"},{"key":"76459_CR63","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1038\/nrc3818","volume":"14","author":"H Yu","year":"2014","unstructured":"Yu, H., Lee, H., Herrmann, A., Buettner, R. & Jove, R. Revisiting STAT3 signalling in cancer: new and unexpected biological functions. Nat. Rev. Cancer 14, 736\u2013746 (2014).","journal-title":"Nat. Rev. Cancer"},{"key":"76459_CR64","doi-asserted-by":"publisher","unstructured":"Witalisz-Siepracka, A., Klein, K., Zd\u00e1rsky, B. & Stoiber, D. The multifaceted role of STAT3 in NK-cell tumor surveillance. Front. Immunol. 13, https:\/\/doi.org\/10.3389\/fimmu.2022.947568 (2022).","DOI":"10.3389\/fimmu.2022.947568"},{"key":"76459_CR65","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1038\/s41698-025-01140-z","volume":"9","author":"Y Wang","year":"2025","unstructured":"Wang, Y. et al. Mechanistic insights into IL-6-mediated NK cell dysfunction in NSCLC via the IRE1\u03b1-XBP1s-STAT3-UBE2S axis. Npj Precis. Onc. 9, 361 (2025).","journal-title":"Npj Precis. Onc."},{"key":"76459_CR66","doi-asserted-by":"crossref","unstructured":"Bonilha, C. S. et al. NET-targeted therapy: effects, limitations, and potential strategies to enhance treatment efficacy. Trends Pharmacol. Sci. 44, 622\u2013634 (2023).","DOI":"10.1016\/j.tips.2023.06.007"},{"key":"76459_CR67","doi-asserted-by":"publisher","first-page":"1532","DOI":"10.1126\/science.1092385","volume":"303","author":"V Brinkmann","year":"2004","unstructured":"Brinkmann, V. et al. Neutrophil extracellular traps kill bacteria. Science 303, 1532\u20131535 (2004).","journal-title":"Science"},{"key":"76459_CR68","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12951-024-02335-5","volume":"22","author":"L Liu","year":"2024","unstructured":"Liu, L. et al. The oncolytic bacteria-mediated delivery system of CCDC25 nucleic acid drug inhibits neutrophil extracellular traps induced tumor metastasis. J. Nanobiotechnol. 22, 69 (2024).","journal-title":"J. Nanobiotechnol."},{"key":"76459_CR69","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/j.jconrel.2023.04.013","volume":"357","author":"Z Wang","year":"2023","unstructured":"Wang, Z. et al. Cell membrane derived liposomes loaded with DNase I target neutrophil extracellular traps which inhibits colorectal cancer liver metastases. J. Control. Release 357, 620\u2013629 (2023).","journal-title":"J. Control. Release"},{"key":"76459_CR70","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.cell.2020.02.015","volume":"180","author":"Y Lu","year":"2020","unstructured":"Lu, Y. et al. Complement signals determine opposite effects of B cells in chemotherapy-induced immunity. Cell 180, 1081\u20131097 (2020).","journal-title":"Cell"},{"key":"76459_CR71","doi-asserted-by":"publisher","first-page":"100086","DOI":"10.1016\/j.xpro.2020.100086","volume":"1","author":"M Charni-Natan","year":"2020","unstructured":"Charni-Natan, M. & Goldstein, I. Protocol for primary mouse hepatocyte isolation. STAR Protoc. 1, 100086 (2020).","journal-title":"STAR Protoc."},{"key":"76459_CR72","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/s41586-019-1410-1","volume":"572","author":"AM Paczulla","year":"2019","unstructured":"Paczulla, A. M. et al. Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion. Nature 572, 254\u2013259 (2019).","journal-title":"Nature"},{"key":"76459_CR73","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s13046-018-1003-0","volume":"38","author":"S Li","year":"2019","unstructured":"Li, S. et al. Tumor-associated neutrophils induce EMT by IL-17a to promote migration and invasion in gastric cancer cells. J. Exp. Clin. Cancer Res. 38, 6 (2019).","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"76459_CR74","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1016\/j.molonc.2014.06.016","volume":"8","author":"S-K Kim","year":"2014","unstructured":"Kim, S.-K. et al. A nineteen gene-based risk score classifier predicts prognosis of colorectal cancer patients. Mol. Oncol. 8, 1653\u20131666 (2014).","journal-title":"Mol. Oncol."},{"key":"76459_CR75","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1200\/JCO.2006.07.4187","volume":"25","author":"M Del Rio","year":"2007","unstructured":"Del Rio, M. et al. Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan. J. Clin. Oncol. 25, 773\u2013780 (2007).","journal-title":"J. Clin. Oncol."},{"key":"76459_CR76","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s10585-012-9532-y","volume":"30","author":"S Barry","year":"2013","unstructured":"Barry, S. et al. S100P is a metastasis-associated gene that facilitates transendothelial migration of pancreatic cancer cells. Clin. Exp. Metastasis 30, 251\u2013264 (2013).","journal-title":"Clin. Exp. Metastasis"},{"key":"76459_CR77","doi-asserted-by":"publisher","first-page":"88","DOI":"10.7150\/ijbs.10583","volume":"11","author":"S Roessler","year":"2015","unstructured":"Roessler, S. et al. Integrative genomic and transcriptomic characterization of matched primary and metastatic liver and colorectal carcinoma. Int. J. Biol. Sci. 11, 88\u201398 (2015).","journal-title":"Int. J. Biol. Sci."},{"key":"76459_CR78","doi-asserted-by":"publisher","first-page":"72908","DOI":"10.18632\/oncotarget.12140","volume":"7","author":"JM Sayagu\u00e9s","year":"2016","unstructured":"Sayagu\u00e9s, J. M. et al. Genomic characterization of liver metastases from colorectal cancer patients. Oncotarget 7, 72908\u201372922 (2016).","journal-title":"Oncotarget"},{"key":"76459_CR79","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41525-021-00223-7","volume":"6","author":"PW Eide","year":"2021","unstructured":"Eide, P. W. et al. Metastatic heterogeneity of the consensus molecular subtypes of colorectal cancer. NPJ Genom. Med. 6, 59 (2021).","journal-title":"NPJ Genom. Med."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-76459-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-76459-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-76459-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:31:18Z","timestamp":1788993078000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-76459-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":79,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["76459"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-76459-7","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"assertion":[{"value":"21 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"9657"}}