{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T02:52:07Z","timestamp":1790218327248,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Natural killer (NK) cell\u2010based therapies show great promise for treating triple\u2010negative breast cancer (TNBC). However, in the tumor microenvironment, some TNBC cells develop resistance to NK cell\u2010mediated killing and contribute to NK cell exhaustion. In this study, TNBC cell populations are isolated that can resist NK cell attacks and uncovered the underlying mechanisms. It is found that these resistant TNBC cells secrete high levels of interleukin\u201011 (IL\u201011). IL\u201011 acts through a process known as trans\u2010signaling by forming complexes with the soluble IL\u201011 receptor (sIL\u201011R) and engaging the gp130 receptor on NK cells. This trans\u2010signaling activates the JAK1\/STAT1\/3 pathway, leading to the upregulation of p21 and subsequent cell cycle arrest in NK cells. As a result, the proliferation and IFN\u03b3 production of NK cells are inhibited, enabling TNBC cells to resist NK cell\u2010mediated killing. Disrupting IL\u201011 or sIL\u201011R in TNBC cells restores NK cell activity. Importantly, it is also found that IL\u201011 expression is elevated in human TNBC tissues and negatively correlated with the number of NK cells in the tumor microenvironment. These findings identify IL\u201011 trans\u2010signaling as a novel mechanism of immune evasion in TNBC and suggest that targeting this pathway may enhance the effectiveness of NK cell\u2010based therapies.<\/jats:p>","DOI":"10.1002\/advs.202515772","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:48:46Z","timestamp":1762163326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Triple\u2010Negative Breast Cancer Cells Resist Natural Killer Cell\u2010Mediated Killing Through Interleukin\u201011 Trans\u2010Signaling"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6352-9067","authenticated-orcid":false,"given":"Hongmei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renfei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7454-9547","authenticated-orcid":false,"given":"Kathy Qian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 999078 China"},{"name":"Ministry of Education Frontiers Science Center for Precision Oncology University of Macau  Taipa Macao SAR 999078 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00565-2"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042420-093238"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1177"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0426-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.903065"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1303605"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.108803"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.4224"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99317"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abl4414"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0432-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.01.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002044"},{"key":"e_1_2_9_14_1","first-page":"1553","author":"Zhao Y.","year":"2015","journal-title":"Onco Targets Ther"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31764-9"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03614-z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0498-z"},{"key":"e_1_2_9_18_1","volume":"12","author":"Du Roure P. D.","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202416811"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg7265"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-021-01691-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2022.114616"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163521"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1478323"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10360"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1007579"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.154.1.180"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.06.010"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202002087R"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03223-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2021.119135"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.01.053"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abc3480"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803694200"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103309"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.01.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14230"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00856-y"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153677"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg6497"},{"key":"e_1_2_9_41_1","first-page":"1727","volume":"118","author":"Ernst M.","year":"2008","journal-title":"J. Clin. Invest."},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-040352"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.07.015"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42754-w"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.06.017"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07701-9"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1004066"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.33.21137"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00716-X"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-024-01808-7"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5262.719"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111486200"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-08-0316"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0132-0"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0511-1"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20220160"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24676"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0066-7"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9060659"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22450-3"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59623"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2016.01.004"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13556"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00132-6"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1594-1"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037361"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0943"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2393"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1515076112"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2022.12.003"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1089\/107999001459123"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.9.2758"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-19-1023"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13650"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515772","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202515772","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202515772","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:00:57Z","timestamp":1769688057000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202515772"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":74,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/advs.202515772"],"URL":"https:\/\/doi.org\/10.1002\/advs.202515772","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"2025-08-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15772"}}