{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:17:09Z","timestamp":1784146629345,"version":"3.55.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32271497"],"award-info":[{"award-number":["32271497"]}],"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":["92478126"],"award-info":[{"award-number":["92478126"]}],"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":["T2450074"],"award-info":[{"award-number":["T2450074"]}],"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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cancer cells present sialylated glycoconjugates that modulate the activity of various immune cells within the tumor microenvironment through <jats:italic>trans<\/jats:italic> interaction with immunosuppressive Siglec receptors. Identifying counter receptors for Siglecs can provide valuable targets for cancer immunotherapy, but it presents significant challenges. Here, the identification of DSG2 (Desmoglein 2) as a dominant counter receptor of Siglec\u20109 in melanoma cells is reported, using a workflow that combines the strength of proximity labeling and the advantage of CRISPR knockout screening. It is further demonstrated that the interaction between DSG2 and Siglec\u20109 is mainly dependent on sialic acid\u2010bearing <jats:italic>N<\/jats:italic>\u2010glycans on DSG2. Importantly, blocking <jats:italic>trans<\/jats:italic> interaction between DSG2 and Siglec\u20109 significantly enhances macrophage phagocytosis of melanoma cells and, to a lesser extent, other cancer cells. The work thus suggests sialylated DSG2 as a potential \u201cdon't eat me\u201d signal molecule with therapeutic potentials in cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/advs.202406654","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T13:32:28Z","timestamp":1736947948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proximity Labeling and Genetic Screening Reveal that DSG2 is a Counter Receptor of Siglec\u20109 and Suppresses Macrophage Phagocytosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Ying","family":"Wu","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyu","family":"You","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingsong","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"He","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchi","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Sun Yat\u2010sen University Cancer Center  Guangzhou 510275 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Third Affiliated Hospital of Sun Yat\u2010sen University  Guangzhou 510000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guigen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Human Virology Department of Pathogen Biology and Biosecurity and Key Laboratory of Tropical Disease Control of Ministry of Education Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou 510080 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8360-4843","authenticated-orcid":false,"given":"Yanqiu","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"},{"name":"State Key Laboratory of Anti\u2010Infective Drug Discovery and Development School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9674-1158","authenticated-orcid":false,"given":"Yang","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 510006 China"},{"name":"Guangdong Provincial Key Laboratory of Drug Non\u2010Clinical Evaluation and Research  Guangzhou 510006 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3737"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2056"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-102419-035900"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-009-0372-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002775200"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-11-187302"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.790317"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65899"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3552"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01359-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf5302"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409580111"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-18-0505"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2015024118"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2019.01.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.03.223"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.3c00664"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c08817"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.05.017"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cww086"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.813082"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2022.102395"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.7b00625"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.086"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwx063"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2009206117"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2006951"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio713"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.04.035"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0554-4"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2026102118"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.262438199"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109060200"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.24.9948"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp194"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr8008012"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1532"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.1.193"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.12.032"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10216"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-016-9520-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0560.2003.00122.x"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.04.001"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-007099"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2012408118"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1456-0"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2016.1146070"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwr087"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1608069113"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-0622-x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj1270"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215376120"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.346"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183329"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09220-y"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-22-0763"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90173-6"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.007083"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202406654","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T09:37:33Z","timestamp":1759743453000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202406654"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":59,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/advs.202406654"],"URL":"https:\/\/doi.org\/10.1002\/advs.202406654","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"assertion":[{"value":"2024-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2406654"}}