{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:09:34Z","timestamp":1788768574367,"version":"build-2803163510"},"reference-count":61,"publisher":"Wiley","issue":"50","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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":["82574775"],"award-info":[{"award-number":["82574775"]}],"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":["82104571"],"award-info":[{"award-number":["82104571"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012216"],"award-info":[{"award-number":["2025A1515012216"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2025A1515012841"],"award-info":[{"award-number":["2025A1515012841"]}],"id":[{"id":"10.13039\/501100003453","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cross\u2010presentation of exogenous antigens by dendritic cells (DCs) is essential for initiating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated anti\u2010tumor immunity. DNGR\u20101 (CLEC9A), a C\u2010type lectin receptor on conventional type 1 DCs (cDC1s), facilitates uptake and cytosolic delivery of dead cell\u2013associated antigens. However, no small\u2010molecule modulators of DNGR\u20101 have been reported. Here, we identify fangchinoline\u2014a natural bisbenzylisoquinoline alkaloid\u2014as a small\u2010molecule modulator that enhances antigen cross\u2010presentation in a DNGR\u20101\u2010dependent manner. Functional screening shows fangchinoline promotes MHC\u2010I\u2013restricted cross\u2010presentation and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell priming. It binds a DNGR\u20101 pocket (Trp209, Glu225, Arg226), confirmed by surface plasmon resonance, thermal shift, probe labeling, and mutagenesis. DNGR\u20101 engagement activates the Syk\u2013Nox2 pathway, increasing phagosomal reactive oxygen species and membrane permeabilization to enable cytosolic antigen access. Fangchinoline exerts subset\u2010dependent effects: in GM\u2010CSF\/IL\u20104\u2013derived DCs and endogenous cDC1\u2010associated settings in vivo, it enhances cross\u2010presentation\u2010associated function, whereas in Flt3L\u2010induced DCs with high basal DNGR\u20101 expression it promotes DNGR\u20101\u2010dependent cell death. In melanoma models, fangchinoline synergizes with DC transfer and PD\u20101 blockade to promote CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated tumor control. It enhances antigen\u2010specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation in human DC\u2013T cell co\u2010cultures. Together, these findings establish fangchinoline as a DNGR\u20101\u2010targeting modulator for context\u2010dependent enhancement of anti\u2010tumor immunity.\n                  <\/jats:p>","DOI":"10.1002\/advs.76043","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T08:17:28Z","timestamp":1781165848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting DNGR\u20101 with Fangchinoline Elevates Dendritic Cell Antigen Cross\u2010Presentation\u2010Mediated Antitumor Immunity in Melanoma"],"prefix":"10.1002","volume":"13","author":[{"given":"Yuan","family":"Liao","sequence":"first","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Research Center of Integrated Chinese and Western Medicine The Affiliated Traditional Chinese Medicine Hospital Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Ren","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Luo","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-9454","authenticated-orcid":false,"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Meishan Tianfu New Area People's Hospital  Meishan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingye","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care The Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3654-2640","authenticated-orcid":false,"given":"Jiangyong","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biaoyan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafei","family":"Shi","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1707-5183","authenticated-orcid":false,"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3282-4330","authenticated-orcid":false,"given":"Kun","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Center of Integrative Medicine School of Basic Medical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Pathology and Pathophysiology Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.15087"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20088"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002498\u2010y"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2022.100907"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.030"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.006"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.09.011"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101848"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008257\u20104"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.08.014"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3258"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010020\u201000824\u2010x"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.021"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.025"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.06.006"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adt5899"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541\u2010025\u201001084\u20102"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60660"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318\u2010025\u201000620\u2010z"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13659\u2010020\u201000293\u20107"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107686"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.03.008"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156143"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156484"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.016"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg8802"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00262\u2010024\u201003849\u20105"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010021\u201000741\u20105"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12596"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00331"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100534"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100210\u2010z"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102611\u20103"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2020.101410"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03059"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1213629"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.03.012"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000448\u20105"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201054650\u2010y"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.05.018"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010002054"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2765"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2017.1307487"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011088"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.11.021"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010022\u201000544\u20104"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adq1405"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010024\u201000859\u20101"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010025\u201008758\u2010w"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.05.021"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan8423"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2017.06.007"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102795"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113506"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep22064"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101726"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010024\u201000785\u20105"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.24.00032"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107628"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2019.03.003"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76043","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76043","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76043","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T07:39:14Z","timestamp":1788766754000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76043"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":61,"journal-issue":{"issue":"50","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.76043"],"URL":"https:\/\/doi.org\/10.1002\/advs.76043","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]},"assertion":[{"value":"2025-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76043"}}