{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:28Z","timestamp":1791262528314,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"9","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":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tertiary lymphoid structures (TLSs) modulate immune responses in various solid tumors, but their comprehensive role in lung adenocarcinoma (LUAD) remains unclear. In this study, we analyzed RNA\u2010seq data from 539 LUAD patients in The Cancer Genome Atlas (TCGA) and microarray data from 223 samples from the Gene Expression Omnibus (GEO, GSE13213, and GSE37745). TLS signatures were evaluated via unsupervised consensus clustering based on 12 chemokine transcriptome signatures. The relationships between TLS and clinical characteristics, tumor microenvironment (TME) cell infiltration, and prognosis were assessed using ESTIMATE and CIBERSORT. A prognostic model was established using LASSO regression and validated with external datasets. Additionally, H&amp;E and IHC analyses were performed to explore associations between intratumoral TLS density, immune\u2010related molecular expression, and patient prognosis in LUAD. Consensus clustering of the TCGA cohort revealed two distinct LUAD patient clusters according to TLS abundance. Cluster 1 exhibited greater immune cell infiltration, more favorable prognosis, and increased expression of immune checkpoint molecules. We developed a prognostic model comprising eight survival\u2010associated genes that act as independent prognostic factors for patient survival. H&amp;E\/IHC analyses revealed that TLS density\u2014regardless of pathological stage\u2014was associated with better prognosis; higher intratumoral TLS density\/proportion was also related to more favorable outcomes. IHC confirmed that survival\u2010associated genes (CD5, HLA\u2010DMB, and P2RY13) are independent prognostic indicators in LUAD. Our study demonstrated the close relationship between TLS signatures and an active immune microenvironment, highlighting their potential as independent prognostic indicators in LUAD.<\/jats:p>","DOI":"10.1002\/cam4.72181","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:16:18Z","timestamp":1788326178000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Tertiary Lymphoid Structures on Immune Cell Infiltration in the Tumor Microenvironment and Prognosis in Lung Adenocarcinoma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8778-5424","authenticated-orcid":false,"given":"Sihong","family":"Le","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidan","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitao","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Urology The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Jiangxi Medical College, Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(15)01281\u20107"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtho.2021.11.003"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2018.78.3118"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801946"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-0593"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.04.014"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010019\u20100144\u20106"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf9419"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201021\u20101130"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00491"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05771-9"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13568"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010019\u20101914\u20108"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001821\u20103"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.674565"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1063711"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2017.43"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.694079"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B2200605"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1789"},{"issue":"24","key":"e_1_2_13_24_1","first-page":"8794","article-title":"The Dynamics of the T\u2010Cell Antitumor Response: Chemokine\u2010Secreting Dendritic Cells Can Prime Tumor\u2010Reactive T Cells Extranodally","volume":"61","author":"Kirk C. 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