{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:05:00Z","timestamp":1786122300983,"version":"build-2736575974"},"reference-count":66,"publisher":"Wiley","issue":"44","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Triple\u2010negative breast cancer (TNBC) is the most aggressive breast cancer subtype with high metastatic potential and limited treatment options. Natural killer (NK) cells represent a promising immunotherapy strategy due to their innate tumor\u2010killing capacity, but their efficacy against TNBC remains limited. We found that TNBC cells, particularly the mesenchymal\u2010like subtype, exhibited greater resistance to NK cells compared to non\u2010TNBC cells. Mechanistic studies indicate that TNBC cells\u2019 survival in response to NK cells occurs in three phases. First, within 1\u00a0h of NK cell\u00a0co\u2010culture, TNBC cells accumulate reactive oxygen species (ROS), which upregulate C\u2010X\u2010C motif chemokine ligand 1 (CXCL1) and interleukin 8 (IL8) expression in an NF\u2010\u03baB\u2212 and ERK\/JNK\u2212AP\u20101\u2010dependent manner. Second, secreted CXCL1\/IL8 binds to C\u2010X\u2010C motif chemokine receptor 1\/2 (CXCR1\/2), activating the AKT\u2212BCL\u20102 pathway to enhance cancer cell survival and suppress NK cell function by downregulating NKG2D, TRAIL, and IFN\u2010\u03b3 expression. Third, CXCL1\/IL8\u2212CXCR1\/2 autocrine loop further amplifies their own synthesis and induces programmed cell death 1 ligand 1 (PD\u2010L1) expression via NF\u2010\u03baB and ERK\/JNK\u2212AP\u20101 pathways. High CXCL1\/IL8 expression correlates with reduced NK cell infiltration and shorter distant\u2010metastasis\u2010free survival in breast cancer patients. Combinatorial application of CXCR1\/2 inhibitor with anti\u2010PD\u2010L1 antibody can overcome NK cell dysfunction and reduce TNBC metastasis.<\/jats:p>","DOI":"10.1002\/advs.75655","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T01:40:37Z","timestamp":1779759637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triple\u2010Negative Breast Cancer Cells Utilize IL8 and CXCL1 to Suppress NK Cells\u2019 Function and Facilitate Cancer Metastasis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4138-8641","authenticated-orcid":false,"given":"Mingheng","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR 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 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangpeng","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuxia","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR China"},{"name":"Ministry of Education Frontiers Science Center For Precision Oncology University of Macau Taipa Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy Qian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Faculty of Health Sciences University of Macau Taipa Macao SAR China"},{"name":"Ministry of Education Frontiers Science Center For Precision Oncology University of Macau Taipa Macao SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201006\u20103045"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153697"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/BTT.S426392"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010025\u201002338\u20102"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010024\u201001955\u20105"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010025\u201002280\u20101"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.MR0218\u2010056RR"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpt.2022.12.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13040857"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010025\u201003375\u2010x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201004279\u20102"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.103348"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12921"},{"key":"e_1_2_9_16_1","first-page":"cm6","article-title":"Natural Killer Cell Receptor Signaling Pathway in Mammals","volume":"2005","author":"Vely F.","year":"2005","journal-title":"Science's STKE"},{"key":"e_1_2_9_17_1","article-title":"Natural Killer Cells in Healthy and Diseased Subjects","volume":"2011","author":"Joyce M. 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