{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:15:54Z","timestamp":1790878554334,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K23373"],"award-info":[{"award-number":["24K23373"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K23504"],"award-info":[{"award-number":["24K23504"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["25K19724"],"award-info":[{"award-number":["25K19724"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Gastroent Surgery"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tertiary lymphoid structures (TLS), clusters of immune cells including B and T cells, are involved in anti\u2010tumor immunity and correlate with a favorable prognosis in several malignancies, but their association with systemic chemotherapy is unknown. We investigated the role of TLS as a biomarker for predicting chemotherapy efficacy in advanced colorectal cancer (CRC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed 78 CRC cases with metastatic or recurrent lesions, in which untreated resected primary tumors were available before chemotherapy. TLS maturity, defined by the presence of CD23\n                      <jats:sup>+<\/jats:sup>\n                      B cells in germinal centers, was assessed by immunohistochemistry and evaluated in relation to clinicopathological features, treatment response, tumor\u2010infiltrating lymphocytes, and prognosis. In 11 cases with resected metastatic lesions, tumor\u2010infiltrating lymphocytes were analyzed to explore the relationship between TLS maturity in primary tumors and immune status at distant sites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mature TLS\u2010negative groups had poorer chemotherapy sensitivity, progression\u2010free survival, and overall survival. Multivariate analysis confirmed TLS maturity as an independent predictor of both therapeutic response and survival outcomes in this cohort. Mature TLS was associated with higher CD3\n                      <jats:sup>+<\/jats:sup>\n                      and CD8\n                      <jats:sup>+<\/jats:sup>\n                      T\u2010cell infiltration in both primary and metastatic tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Mature TLS may contribute to favorable chemotherapeutic efficacy through immune activity. TLS maturity in primary tumors may represent a novel biomarker for predicting systemic chemotherapy response and immune status across primary and metastatic sites in advanced CRC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ags3.70142","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T06:48:35Z","timestamp":1764744515000},"page":"710-721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mature Tertiary Lymphoid Structures Indicate Good Chemotherapy Response and Prognosis in Advanced Colorectal Cancer"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4381-4703","authenticated-orcid":false,"given":"Nobuhiro","family":"Hosoi","sequence":"first","affiliation":[{"name":"Department of General Surgical Science Gunma University Graduate School of Medicine  Maebashi 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