{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:19:08Z","timestamp":1788265148271,"version":"build-2803163510"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"abstract":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n Although tertiary lymphoid structures (TLSs) contribute to antitumor immunity, the significance of CD86 expression within mature TLSs in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study evaluated CD86\u2010positive mature TLSs as a marker of an immunologically active tumor microenvironment.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed 128 treatment\u2010naive patients with PDAC who underwent curative resection. TLSs were evaluated by hematoxylin and eosin staining and immunohistochemistry for CD4, CD8, CD20, CD21, CD23, and CD86. TLS maturation, CD86 expression, TLS density and diameter, intratumoral T\u2010cell infiltration, and clinical outcomes were assessed. Multiplex immunofluorescence for CD8 and Granzyme B was performed in selected cases.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n TLSs were identified in 124 patients. Among TLS\u2010positive cases, 13, 21, and 90 were classified as immature, intermediate, and mature TLSs, respectively. Mature TLSs were associated with increased intratumoral CD8\n +<\/jats:sup>\n T\u2010cell infiltration compared with TLS\u2010absent cases (\n p<\/jats:italic>\n \u2009=\u20090.027), whereas CD4\n +<\/jats:sup>\n T\u2010cell infiltration did not differ significantly. CD86\u2010positive mature TLSs were associated with higher intratumoral CD8\n +<\/jats:sup>\n T\u2010cell infiltration (\n p<\/jats:italic>\n \u2009=\u20090.002), greater TLS density, and larger TLS diameter than CD86\u2010negative mature TLSs. Multiplex immunofluorescence confirmed that most CD86\u2010positive cells co\u2010expressed CD20. Exploratory CD8\/Granzyme B analysis suggested a higher proportion of Granzyme B\u2010expressing CD8\n +<\/jats:sup>\n T cells in CD86\u2010positive mature TLSs. Patients with CD86\u2010positive mature TLSs showed favorable clinical outcomes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n CD86\u2010positive mature TLSs may represent a pathological feature associated with an immunologically active tumor microenvironment in PDAC, as reflected by increased intratumoral CD8\n +<\/jats:sup>\n T\u2010cell infiltration, a higher proportion of Granzyme B\u2010expressing CD8\n +<\/jats:sup>\n T cells in the exploratory analysis, and favorable clinical outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ags3.70275","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:56Z","timestamp":1788263456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD86<\/scp>\n \u2010Positive Mature Tertiary Lymphoid Structures Are Associated With\n CD8<\/scp>\n +<\/sup>\n T\u2010Cell Infiltration and Favorable Clinical Outcomes in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0915-6127","authenticated-orcid":false,"given":"Takaomi","family":"Seki","sequence":"first","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-4551","authenticated-orcid":false,"given":"Kenichiro","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3284-4796","authenticated-orcid":false,"given":"Takehiko","family":"Yokobori","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy Science Gunma University, Initiative for Advanced Research (GIAR) Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0289-314X","authenticated-orcid":false,"given":"Hayato","family":"Ikota","sequence":"additional","affiliation":[{"name":"Clinical Department of Pathology Gunma University Hospital Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2624-2529","authenticated-orcid":false,"given":"Norio","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9077-2052","authenticated-orcid":false,"given":"Takamichi","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3748-9615","authenticated-orcid":false,"given":"Mariko","family":"Tsukagoshi","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6591-2439","authenticated-orcid":false,"given":"Norihiro","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Surgery and Laparoscopic Surgery Gunma Prefecture Saiseikai Maebashi Hospital Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Hosouchi","sequence":"additional","affiliation":[{"name":"Department of Surgery and Laparoscopic Surgery Gunma Prefecture Saiseikai Maebashi Hospital Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7173-7945","authenticated-orcid":false,"given":"Ken","family":"Shirabe","sequence":"additional","affiliation":[{"name":"Department of General Surgical Science Gunma University, Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"issue":"6","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1002\/ags3.12835","article-title":"Incidence, Mortality, Survival, and Treatment Statistics of Cancers in Digestive Organs\u2010Japanese Cancer Statistics 2024","volume":"8","author":"Higashi 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A.","year":"2022","journal-title":"Journal of Clinical Oncology"},{"issue":"1","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-024-02097-4","article-title":"Digestive Cancers: Mechanisms, Therapeutics and Management","volume":"10","author":"Zhan T.","year":"2025","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"6576","key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.abf9419","article-title":"Tertiary Lymphoid Structures in Cancer","volume":"375","author":"Schumacher T. N.","year":"2022","journal-title":"Science"},{"issue":"15","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers16152684","article-title":"A Mature Tertiary Lymphoid Structure With a Ki\u201067\u2010Positive Proliferating Germinal Center Is Associated With a Good Prognosis and High Intratumoral Immune Cell Infiltration in Advanced Colorectal Cancer","volume":"16","author":"Mori N.","year":"2024","journal-title":"Cancers"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ags3.70142"},{"issue":"12","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1038\/s41416-023-02235-9","article-title":"Density and Maturity of Peritumoral Tertiary Lymphoid Structures in Oesophageal Squamous Cell Carcinoma Predicts Patient Survival and Response to Immune Checkpoint Inhibitors","volume":"128","author":"Hayashi Y.","year":"2023","journal-title":"British Journal of Cancer"},{"issue":"4","key":"e_1_2_13_9_1","doi-asserted-by":"crossref","DOI":"10.1093\/pcmedi\/pbae030","article-title":"Comparative Analysis of Tertiary Lymphoid Structures for Predicting Survival of Colorectal Cancer: A Whole\u2010Slide Images\u2010Based Study","volume":"7","author":"He M.","year":"2024","journal-title":"Precision Clinical Medicine"},{"issue":"9","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1002\/ijc.28533","article-title":"Characteristics and Significance of Colorectal Cancer Associated Lymphoid Reaction","volume":"134","author":"V\u00e4yrynen J. P.","year":"2014","journal-title":"International Journal of Cancer"},{"issue":"11","key":"e_1_2_13_11_1","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1038\/bjc.2015.145","article-title":"Intratumoral Tertiary Lymphoid Organ Is a Favourable Prognosticator in Patients With Pancreatic Cancer","volume":"112","author":"Hiraoka N.","year":"2015","journal-title":"British Journal of Cancer"},{"issue":"6","key":"e_1_2_13_12_1","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1111\/cas.14023","article-title":"Prognostic Relevance of Tertiary Lymphoid Organs Following Neoadjuvant Chemoradiotherapy in Pancreatic Ductal Adenocarcinoma","volume":"110","author":"Kuwabara S.","year":"2019","journal-title":"Cancer Science"},{"issue":"1","key":"e_1_2_13_13_1","doi-asserted-by":"crossref","DOI":"10.1080\/2162402X.2021.1900635","article-title":"Germinal Center Reactions in Tertiary Lymphoid Structures Associate With Neoantigen Burden, Humoral Immunity and Long\u2010Term Survivorship in Pancreatic Cancer","volume":"10","author":"Gunderson A. J.","year":"2021","journal-title":"Oncoimmunology"},{"issue":"6","key":"e_1_2_13_14_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-006698","article-title":"Characterization of Intratumoral Tertiary Lymphoid Structures in Pancreatic Ductal Adenocarcinoma: Cellular Properties and Prognostic Significance","volume":"11","author":"Zou X.","year":"2023","journal-title":"Journal for Immunotherapy of Cancer"},{"issue":"3","key":"e_1_2_13_15_1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00535-022-01939-8","article-title":"Integrated Analysis of Tertiary Lymphoid Structures in Relation to Tumor\u2010Infiltrating Lymphocytes and Patient Survival in Pancreatic Ductal Adenocarcinoma","volume":"58","author":"Tanaka T.","year":"2023","journal-title":"Journal of Gastroenterology"},{"issue":"9","key":"e_1_2_13_16_1","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1158\/2326-6066.CIR-20-0949","article-title":"CD86+Antigen\u2010Presenting b Cells Are Increased in Cancer, Localize in Tertiary Lymphoid Structures, and Induce Specific T\u2010Cell Responses","volume":"9","author":"Wennhold K.","year":"2021","journal-title":"Cancer Immunology Research"},{"issue":"3","key":"e_1_2_13_17_1","doi-asserted-by":"crossref","first-page":"e528","DOI":"10.1097\/SLA.0000000000005104","article-title":"Immunoscore Signatures in Surgical Specimens and Tumor\u2010Infiltrating Lymphocytes in Pretreatment Biopsy Predict Treatment Efficacy and Survival in Esophageal Cancer","volume":"277","author":"Noma T.","year":"2023","journal-title":"Annals of Surgery"},{"issue":"1","key":"e_1_2_13_18_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/ags3.70090","article-title":"Outcomes of Resected Cases of Pancreatic Ductal Adenocarcinoma Patients With Unexpected Postoperative Uncovering Noncurative Factors: A Multicenter Retrospective Study","volume":"10","author":"Matsui H.","year":"2025","journal-title":"Annals of Gastroenterological Surgery"},{"issue":"13","key":"e_1_2_13_19_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.954936","article-title":"Role of B Cells as Antigen Presenting Cells","volume":"8","author":"Rastogi I.","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"2","key":"e_1_2_13_20_1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1189\/jlb.5A0416-182R","article-title":"Antigen\u2010Presenting Human B Cells Are Expanded in Inflammatory Conditions","volume":"101","author":"Shimabukuro\u2010Vornhagen A.","year":"2017","journal-title":"Journal of Leukocyte Biology"},{"issue":"3","key":"e_1_2_13_21_1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ccell.2023.02.017","article-title":"B Cells in the Tumor Microenvironment: Multi\u2010Faceted Organizers, Regulators, and Effectors of Anti\u2010Tumor Immunity","volume":"41","author":"Laumont C. M.","year":"2023","journal-title":"Cancer Cell"},{"key":"e_1_2_13_22_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1146\/annurev-immunol-101220-015603","article-title":"B Cell Function in the Tumor Microenvironment","volume":"40","author":"Downs\u2010Anner S. M.","year":"2022","journal-title":"Annual Review of Immunology"},{"issue":"7","key":"e_1_2_13_23_1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.hpb.2024.04.009","article-title":"Impact of Tertiary Lymphoid Structures on Prognosis and Therapeutic Response in Pancreatic Ductal Adenocarcinoma","volume":"26","author":"Merali N.","year":"2024","journal-title":"HPB"},{"issue":"14","key":"e_1_2_13_24_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1222719","article-title":"Tertiary Lymphoid Structures in Pancreatic Cancer: A New Target for Immunotherapy","volume":"17","author":"Zou X.","year":"2023","journal-title":"Frontiers in Immunology"},{"issue":"4","key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1158\/2326-6066.CIR-22-0121","article-title":"Tissue\u2010Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD\u20101 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade","volume":"11","author":"Pearce H.","year":"2023","journal-title":"Cancer Immunology Research"},{"issue":"12","key":"e_1_2_13_26_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.696311","article-title":"The Impact of Programmed Cell Death on the Formation of Tertiary Lymphoid Structures","volume":"15","author":"Dieud\u00e9 M.","year":"2021","journal-title":"Frontiers in Immunology"},{"issue":"5","key":"e_1_2_13_27_1","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1158\/0008-5472.CAN-17-1987","article-title":"Germinal Centers Determine the Prognostic Relevance of Tertiary Lymphoid Structures and Are Impaired by Corticosteroids in Lung Squamous Cell Carcinoma","volume":"78","author":"Sili\u0146a K.","year":"2018","journal-title":"Cancer Research"},{"issue":"1","key":"e_1_2_13_28_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41392-024-01947-5","article-title":"Tertiary Lymphoid Structures in Diseases: Immune Mechanisms and Therapeutic Advances","volume":"9","author":"Zhao L.","year":"2024","journal-title":"Signal Transduction and Targeted Therapy"},{"issue":"12","key":"e_1_2_13_29_1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.736670","article-title":"High Endothelial Venules: A Vascular Perspective on Tertiary Lymphoid Structures in Cancer","volume":"17","author":"Vella G.","year":"2021","journal-title":"Frontiers in Immunology"},{"issue":"5","key":"e_1_2_13_30_1","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1016\/j.jcmgh.2021.06.023","article-title":"Pancreatic Cancer Chemotherapy Is Potentiated by Induction of Tertiary Lymphoid Structures in Mice","volume":"12","author":"Delvecchio F. R.","year":"2021","journal-title":"Cellular and Molecular Gastroenterology and Hepatology"}],"container-title":["Annals of Gastroenterological Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ags3.70275","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ags3.70275","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ags3.70275","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:59Z","timestamp":1788263459000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ags3.70275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":29,"alternative-id":["10.1002\/ags3.70275"],"URL":"https:\/\/doi.org\/10.1002\/ags3.70275","archive":["Portico"],"relation":{},"ISSN":["2475-0328","2475-0328"],"issn-type":[{"value":"2475-0328","type":"print"},{"value":"2475-0328","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ags3.70275"}}