{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T16:11:19Z","timestamp":1791562279527,"version":"4.3.4"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T00:00:00Z","timestamp":1763251200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NSFC82173155"],"award-info":[{"award-number":["NSFC82173155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372823"],"award-info":[{"award-number":["82372823"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273295"],"award-info":[{"award-number":["82273295"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>\n                    Tumor\u2010related metabolites in the tumor microenvironment may induce immune dysfunction, leading to malignant progression and metastasis of tumors. Here, it is demonstrated that tumoral PLA2G16, a phospholipase catalyzes phospholipids to generate free fatty acid (FFA) or lysophosphatidic acid (LPA), is an important contributor to triple\u2010negative breast cancer (TNBC) lung metastasis in an immune\u2010dependent pattern by improving tetracosatetraenoic acid (C24:4 (n\u20106)) accumulation in the early metastatic niche of lung and impairing immune function of pulmonary CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. C24:4 (n\u20106) induces nuclear import of PPAR\u03b1 in pneumal CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which regulates the transcription of\n                    <jats:italic>Cpt1a, Dgat1, Cd36<\/jats:italic>\n                    , and\n                    <jats:italic>Fabp1<\/jats:italic>\n                    , leading to the activation of fatty acid oxidation (FAO). The robust FAO results in suppression of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Genetically depleting PPAR\u03b1 in mice, pharmacologically inhibiting C24:4 (n\u20106)\u2010induced PPAR\u03b1 in the nucleus or directly suppressing PPAR\u03b1 activity effectively attenuates PLA2G16\u2010C24:4 (n\u20106) axis\u2010based immune dysfunction of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and their according anti\u2010tumor activities. These results imply that PLA2G16\u2010mediated C24:4 (n\u20106) accumulation in the lung acts as a metabolic disorder to CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell antitumor activity and highlights a critical role of PLA2G16 in promoting TNBC lung metastasis. Targeting PLA2G16 and combination with anti\u2010PD\u20101\u2010based immunotherapy may be an effective strategy for clinical tumor immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202510224","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T16:30:28Z","timestamp":1763310628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["PLA2G16\u2010Mediated Tetracosatetraenoic Acid Rewires Fatty Acid Oxidation to Impair CD8\n                    <sup>+<\/sup>\n                    T Cell Immune Function in Promoting Breast Cancer Lung Metastasis"],"prefix":"10.1002","volume":"13","author":[{"given":"Yubi","family":"Gan","sequence":"first","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Die","family":"Meng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Lang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology College of Basic Medicine Molecular Medicine Diagnostic and Testing Center Chongqing Medical University Department of Pathology The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijin","family":"Dai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Chang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zexiu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuetong","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanchun","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine The First Affiliated Hospital of Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Hou","sequence":"additional","affiliation":[{"name":"Experimental Teaching Center of Basic Medicine Science Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Tan","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center Chongqing Medical University  Chongqing 400016 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-6878","authenticated-orcid":false,"given":"Manran","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Clinical Laboratory Medical Diagnostics Chinese Ministry of Education Chongqing Medical University  Chongqing 400016 China"},{"name":"Western Institute of Digital Intelligent Medicine  Chongqing 401329 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,16]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2014.10.009"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2569"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8931"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1815515116"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00565-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2499-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.34133\/research.0289"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0273-y"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00317-z"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.04.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-19-2994"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.04.002"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93411"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.08.002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33349-y"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20191920"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01949"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205377"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1904"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202060"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804146200"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.08.137"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2014.01.007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28438-x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15832"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.7694"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.009"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01194-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-023-02928-2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00817-8"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.02.013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.042"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2020.11.027"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.458372"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.05.001"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-022-01017-3"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1987211"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2891-13-17"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0316"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840400405"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31764-9"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.004"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.01.038"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.06.081"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00339-z"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.04.017"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.12.006"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-023-00513-2"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24142545"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00064"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3838"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0365-3"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.004"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.06.007"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.018"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.07.008"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803510"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0095"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.08.004"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202510224","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202510224","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202510224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:46:36Z","timestamp":1775979996000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202510224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,16]]},"references-count":64,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/advs.202510224"],"URL":"https:\/\/doi.org\/10.1002\/advs.202510224","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,16]]},"assertion":[{"value":"2025-06-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e10224"}}