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Here, a single\u2010cell glycomic profiling strategy was applied to tumor tissues from patients with pancreatic ductal adenocarcinoma (PDAC), enabling the identification of cell\u2010type\u2010specific glycome signatures and their dynamic alterations during the transition from classical to basal\u2010like cancer subtypes. To systematically decode glycan\u2010mediated communication in the TME, an analytical framework termed GlycoChat was developed for mapping global glycan\u2013lectin circuits at single\u2010cell resolution. GlycoChat identified CLEC10A and SIGLEC3 as lectin receptors expressed on tumor\u2010associated macrophages that interact with cancer cell surface glycans. Functional assays demonstrated that cancer cells promote differentiation of immunosuppressive macrophages and impair phagocytic activity through interactions with CLEC10A and SIGLEC3. This study establishes GlycoChat as a powerful tool for dissecting glycan\u2013lectin circuits in complex TME and highlights glyco\u2010immune checkpoints as potential targets for therapeutic intervention in PDAC.<\/jats:p>","DOI":"10.1002\/advs.202514735","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T10:41:48Z","timestamp":1768387308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["GlycoChat Uncovers Glycan\u2013Lectin Circuits in the Tumor Microenvironment of Pancreatic Cancer"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6126-6259","authenticated-orcid":false,"given":"Dinh Xuan Tuan","family":"Anh","sequence":"first","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Tsukuba Ibaraki Japan"},{"name":"Ph.D. Program in Human Biology School of Integrative and Global Majors University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunanda","family":"Keisham","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Burramsetty","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lalhaba","family":"Oinam","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Kumano","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Kuno","sequence":"additional","affiliation":[{"name":"Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"},{"name":"Laboratory Animal Resource Center Transborder Medical Research Center Institute of Medicine University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Shimomura","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and Hepato\u2010Biliary\u2010Pancreatic Surgery Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3006-1659","authenticated-orcid":false,"given":"Hiroaki","family":"Tateno","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute National Institute of Advanced Industrial Science and Technology (AIST)  Tsukuba Ibaraki Japan"},{"name":"Institute of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201073525\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201014\u20100155"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv295"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0000000000000288"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11060901"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1258538"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1116016"},{"key":"e_1_2_10_9_1","volume-title":"Essentials of Glycobiology [Internet]","author":"Varki A.","year":"2015"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M114.047837"},{"key":"e_1_2_10_11_1","first-page":"5489","article-title":"Identification of the Gastrointestinal and Pancreatic Cancer\u2010Associated Antigen Detected by Monoclonal Antibody 19\u20139 in the Sera of Patients as a Mucin","volume":"43","author":"Magnani J. 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