{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:51:18Z","timestamp":1789487478526,"version":"build-2803163510"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"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":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cells and LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      dendritic cells (DCs) are pivotal players in orchestrating anti\u2010tumor immune responses, particularly within tumor tertiary lymphoid structures (TLS). However, their heterogeneity, differentiation trajectories, and clinical relevance in bladder cancer remain incompletely defined.\n                    <\/jats:p>\n                    <jats:p>\n                      This study integrated single\u2010cell RNA sequencing (scRNA\u2010seq) data (16 bladder cancer patients, 113,905 post\u2010quality\u2010control cells) and spatial transcriptomics to characterize CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cell\/LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      DC subsets, their differentiation pathways (via Velocyto trajectory analysis), and intercellular crosstalk (via receptor\u2010ligand mapping). A risk model (DTscore) was constructed using marker genes of these cells and validated in the IMvigor210 (atezolizumab\u2010treated bladder cancer) and TCGA\u2010BLCA cohorts.\n                    <\/jats:p>\n                    <jats:p>\n                      scRNA\u2010seq clustering identified 10 immune and 3 nonimmune cell types, with T cells stratified into 8 subpopulations (including CD4\n                      <jats:sup>+<\/jats:sup>\n                      CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cells and CD8\n                      <jats:sup>+<\/jats:sup>\n                      CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cells) and DCs into 9 subgroups (including LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      DCs). Receptor\u2010ligand mapping and spatial transcriptomics confirmed functional crosstalk between CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cells and LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      DCs via key pairs (e.g., CCR7\u2010CCL19, CXCR5\u2010CXCL13, PDCD1\u2010CD274) within TLS. The DTscore was developed using 8 marker genes (TSHZ2, ALOX5AP, GADD45G, TXN, CHN1, CCL19, CXCL13, ICA1) and exhibited robust prognostic and predictive performance: In the IMvigor210 cohort, high DTscore correlated with significantly poorer overall survival (OS) and a 3.27\u2010fold lower immunotherapy response rate (11% vs. 36%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20094.23e\u201007); multivariate Cox regression confirmed DTscore as an independent OS predictor (hazard ratio\u2009=\u20091.97,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). DTscore retained prognostic value in TCGA\u2010BLCA (OS:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003; disease\u2010specific survival:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and effectively predicted atezolizumab response even in the \u201cimmune desert\u201d phenotype (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Combining DTscore with tumor mutational burden\/tumor neoantigen burden yielded an AUC of 0.8122 for response prediction. Additionally, high DTscore was associated with higher OS hazard ratios in patients with wild\u2010type TTN, RB1, EP300,\n                      <jats:italic>or<\/jats:italic>\n                      FGFR3 (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while\n                      <jats:italic>FGFR3<\/jats:italic>\n                      mutations correlated with lower immune checkpoint\/CXCL13 expression.\n                    <\/jats:p>\n                    <jats:p>\n                      This study delineates the heterogeneity and interactions of CXCL13\n                      <jats:sup>+<\/jats:sup>\n                      T cell\/LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      DC subsets in bladder cancer TLS and validates DTscore as a robust tool for predicting OS and immunotherapy response, offering a potential guide for personalized bladder cancer treatment.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.70162","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T14:53:06Z","timestamp":1785941586000},"page":"1311-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Immunological Analysis of Interactions Between CXCL13+ T Cells and LAMP3+ DC in the Immunotherapy Response of Bladder Cancer"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-6915","authenticated-orcid":false,"given":"Lin","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Urology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-5745","authenticated-orcid":false,"given":"Jinchao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5011-0203","authenticated-orcid":false,"given":"Bin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Urology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai 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