{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:45:15Z","timestamp":1777484715390,"version":"3.51.4"},"reference-count":36,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"crossref","award":["LQ20H160003"],"award-info":[{"award-number":["LQ20H160003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Scientific Research Foundation of Ministry of Public Health of China\/Major Science and Technology Program of Medicine and Health of Zhejiang Province of China","award":["WKJ-ZJ-2451"],"award-info":[{"award-number":["WKJ-ZJ-2451"]}]},{"name":"Clinical Research Expert Training Program Project of Zhoushan Hospital","award":["YJZJ-C21"],"award-info":[{"award-number":["YJZJ-C21"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Tertiary lymphoid structures (TLSs) have been associated with the prognosis of various solid tumors. However, the association between TLSs and the prognosis of invasive lung adenocarcinoma (IAC) remains unclear in terms of location, density, and maturity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively reviewed the clinicopathological characteristics of 750 patients with IAC. The density of TLSs in various tumor regions, as well as their maturation status, was examined by pathologists. The X-tile software was employed to determine the optimal cut-off values for the intratumoral and peritumoral TLS density based on overall survival. A threshold of 1.33 TLSs\/cm\n                      <jats:sup>2<\/jats:sup>\n                      was used to distinguish between low- and high-density intratumoral TLSs, while a threshold of 1.39 TLSs\/cm\n                      <jats:sup>2<\/jats:sup>\n                      was applied for peritumoral TLSs. Tissue slides exhibiting no or early TLSs demonstrated low maturation levels, while those with at least one lymphoid follicle indicated high maturation. We analyzed the correlation between TLS characteristics and clinicopathological parameters and assessed the impact of multiple clinicopathological factors on patient prognosis using Cox regression and Kaplan\u2013Meier analyses. A multivariate logistic regression analysis model was used to explore predictive factors for the density of intratumoral TLSs and TLS maturity in patients with IAC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lower intratumoral TLS density, increased TLS maturation, lymph node metastasis, and the presence of solid (\u226530%) and micropapillary (\u22655%) pathological subtypes were identified as poor independent prognostic factors for overall survival in patients with IAC. Solid (\u226530%) and micropapillary (\u22655%) pathological subtypes were predictive factors for lower intratumoral TLS density (hazard ratio [HR] = 0.434, 95% confidence interval [CI] = 0.267-0.706,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.001), while higher TLSs maturity was associated with a smoking history or pleural invasion (HR = 1.655, 95% CI = 1.048-2.613,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.031; HR = 1.933, 95% CI = 1.054-3.546,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.033).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Both intratumoral TLS density and TLS maturation are independent prognostic factors for IAC. Additionally, higher TLS density predicted better prognosis, whereas greater TLS maturity predicted worse prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10732748251372684","type":"journal-article","created":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T14:23:34Z","timestamp":1756650214000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Density and Maturity of Tertiary Lymphoid Structures Predict Clinical Outcome in Invasive Lung Adenocarcinoma"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-7769","authenticated-orcid":false,"given":"Yanyan","family":"Huang","sequence":"first","affiliation":[{"name":"Cellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhoushan Hospital, Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Li","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinjin","family":"Lou","sequence":"additional","affiliation":[{"name":"Zhoushan Hospital, Postgraduate Training Base Alliance of Wenzhou Medical University, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyun","family":"Xu","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology Laboratory, Zhoushan Hospital, Wenzhou Medical University, Zhoushan, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,8,31]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.0025"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.4932"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2021.12.655"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01830"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1914-8"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-2590"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.693234"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.689270"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep31628"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5731"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-024-12136-6"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.103883"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-019-02407-8"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1987"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1342"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-021-01307-y"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf9419"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-022-09777-w"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6020969"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.91487"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.10.030"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3290"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1097\/JTO.0b013e318287c3eb"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2015.06.004"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-015-5043-9"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31828920c0"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.pap.0000138142.26882.fe"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2021.1900635"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.09.006"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005539"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-15-49"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-2765"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-024-02970-6"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0144-6"}],"container-title":["Cancer 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