{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:52:27Z","timestamp":1781581947284,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFA0915700"],"award-info":[{"award-number":["2023YFA0915700"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Immune checkpoint blockade (ICB) induces durable responses in a subset of breast cancer patients, yet many show limited benefit from anti\u2010PD\u20101\/PD\u2010L1 therapy. Understanding differences in the tumor microenvironment (TME) and tumor\u2010intrinsic immune evasion between responders (R) and nonresponders (NR) is key to improving outcomes. We integrated three public scRNA\u2010seq datasets from PD\u2010(L)1\u2010treated breast cancer (51 patients; 327022 cells) and analyzed paired pre\u2010\/posttreatment samples. Compared to NR, R patients exhibited increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration, enhanced interferon\u2010response activity, and myeloid\/B\u2010cell remodeling. Pseudotime analysis showed T cells in R progressed from activation to cytotoxic differentiation and ultimately exhaustion, consistent with effective ICB response patterns. Through tumor\u2010intrinsic screening, we identified LYPD6B\u2010a membrane gene upregulated in NR cancer cells that suppresses antigen processing\/presentation and IFN\u03b1\/\u03b2 signaling. Functional assays confirmed that LYPD6B ablation impairs proliferation, clonogenic growth, and induces apoptosis. Drug\u2010repurposing analyses revealed venetoclax binds LYPD6B and recapitulates its antiproliferative effects. Immunohistochemistry (IHC) and pan\u2010cancer analyses verified LYPD6B's tumor\u2010cell localization, association with immune infiltration, and checkpoint expression. Collectively, LYPD6B emerges as a tumor\u2010intrinsic mediator of immune evasion and PD\u2010(L)1 resistance, representing a promising target for combination immunotherapy in breast cancer.\n                  <\/jats:p>","DOI":"10.1111\/1759-7714.70311","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:30:22Z","timestamp":1780464622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Analysis Identifies LYPD6B as a Tumor\u2010Intrinsic Candidate Associated With Immunotherapy Nonresponse in Breast Cancer"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6334-4244","authenticated-orcid":false,"given":"Yifei","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Cancer Immunotherapy of Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology  Shenzhen Guangdong China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiwei","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology  Shenzhen Guangdong China"},{"name":"Department of Biomedical Engineering Southern University of Science and Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Cancer Immunotherapy of Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"Department of Biopharmaceutical Sciences, Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809615"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.7147"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30904-X"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-018-0007-y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32531-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0182"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14404"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9935"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.069"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15440"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102329"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1604958"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00911-1"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.03.005"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.060"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.10.038"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0522-3"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.09.010"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-022-0968-4"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.004"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3365"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2025.104971"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-67344-w"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1145\/1970392.1970395"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2015.12.004"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.1c00203"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.8b00462"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20035"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx247"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13048-024-01556-4"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.08.039"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2021.04.014"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.023"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0312-6"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.06.036"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02212-7"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0667-5"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01808-1"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3048"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-023-01232-y"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.022"}],"container-title":["Thoracic Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1759-7714.70311","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1759-7714.70311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:04:57Z","timestamp":1781579097000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1759-7714.70311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/1759-7714.70311"],"URL":"https:\/\/doi.org\/10.1111\/1759-7714.70311","archive":["Portico"],"relation":{},"ISSN":["1759-7706","1759-7714"],"issn-type":[{"value":"1759-7706","type":"print"},{"value":"1759-7714","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"2026-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70311"}}