{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:24:09Z","timestamp":1793744649403,"version":"4.6.1"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Tertiary lymphoid structures (TLSs) are associated with immunotherapy response and survival across solid tumors and are increasingly evaluated as tissue biomarkers. Neoadjuvant treatment provides pretreatment biopsies, on-treatment samples, and surgical resections, but these time points answer different clinical questions. Previous reviews have established TLS biology, maturation, and broad associations with response and survival. Here, we organize the evidence by sampling context, measurement object, and intended use. Pretreatment TLSs are candidate baseline stratification markers; within-patient changes describe pharmacodynamic remodeling only when specimens are comparable; and surgical TLSs describe post-treatment response phenotypes or postoperative prognosis according to the outcome time origin. These roles call for distinct validation designs. Immune cells, stromal organizers, and specialized vasculature can reshape TLSs, but parallel structural and tumor changes do not show that treatment benefit depends on TLSs. TLS-specific loss-and-rescue experiments are still needed to test that causal contribution. Clinical translation should therefore start with the decision being made and align the sample, measurement, missingness rules, and validation design to that decision. This framework explains part of the apparent inconsistency across studies and offers a practical path from descriptive associations to clinically interpretable evidence.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1948933","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:21:11Z","timestamp":1789032071000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tertiary lymphoid structures in neoadjuvant and perioperative cancer immunotherapy: a review and proposed framework for biomarker interpretation and validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Zilin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Zigong First People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingsheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Oncology, Zigong First People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Zigong First People\u2019s Hospital","place":["Zigong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1038\/s43018-021-00232-6","article-title":"Mature tertiary lymphoid structures predict immune checkpoint inhibitor efficacy in solid tumors independently of PD-L1 expression","volume":"2","author":"Vanhersecke","year":"2021","journal-title":"Nat Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1914-8","article-title":"Tertiary lymphoid structures improve immunotherapy and survival in melanoma","volume":"577","author":"Cabrita","year":"2020","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.immuni.2022.02.001","article-title":"Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing plasma cells in renal cell cancer","volume":"55","author":"Meylan","year":"2022","journal-title":"Immunity"},{"key":"B4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s13046-026-03644-3","article-title":"Tertiary lymphoid structures in the era of cancer therapy","volume":"45","author":"Hern\u00e1ndez-Verdin","year":"2026","journal-title":"J Exp Clin Cancer Res CR"},{"key":"B5","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s13045-025-01754-7","article-title":"Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities","volume":"18","author":"Deng","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.7150\/thno.113940","article-title":"Dissecting tertiary lymphoid structures in cancer: maturation, localization and density","volume":"15","author":"Su","year":"2025","journal-title":"Theranostics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00262-025-04183-0","article-title":"Dynamic remodeling of tertiary lymphoid structures in response to cancer therapy: a recent review","volume":"74","author":"Tan","year":"2025","journal-title":"Cancer Immunology Immunotherapy CII"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.71728","article-title":"The emerging role of tertiary lymphoid structures as predictive and prognostic biomarkers of immunotherapy in cancer","volume":"15","author":"Medhin","year":"2026","journal-title":"Cancer Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1882195","article-title":"Tertiary lymphoid structures as biomarkers and therapeutic targets in neoadjuvant cancer immunotherapy","volume":"17","author":"Wang","year":"2026","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1871411","article-title":"An IHC-derived TLS-CD8-macrophage immune niche score predicts major pathological response to neoadjuvant chemoimmunotherapy in resectable NSCLC","volume":"17","author":"Tan","year":"2026","journal-title":"Front Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12447","article-title":"Predictive power of tertiary lymphoid structure signature for neoadjuvant chemotherapy response and immunotherapy benefit in HER2-negative breast cancer","volume":"43","author":"Bertucci","year":"2023","journal-title":"Cancer Commun (London England)"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-22-2566","article-title":"A phase II window of opportunity study of neoadjuvant PD-L1 versus PD-L1 plus CTLA-4 blockade for patients with Malignant pleural mesothelioma","volume":"29","author":"Lee","year":"2023","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005531","article-title":"Maturation and abundance of tertiary lymphoid structures are associated with the efficacy of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer","volume":"10","author":"Sun","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.71889","article-title":"Neoadjuvant immunochemotherapy increases the abundance of tertiary lymphoid structures and lymphocyte subpopulations is associated with prognosis of esophageal squamous cell carcinoma","volume":"15","author":"Li","year":"2026","journal-title":"Cancer Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.675146","article-title":"A standardized analysis of tertiary lymphoid structures in human melanoma: disease progression- and tumor site-associated changes with germinal center alteration","volume":"12","author":"Werner","year":"2021","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2023.100063","article-title":"Standardized pathology screening of mature tertiary lymphoid structures in cancers","volume":"103","author":"Vanhersecke","year":"2023","journal-title":"Lab Investigation; A J Tech Methods Pathol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41392-024-02029-2","article-title":"Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial","volume":"9","author":"Liu","year":"2024","journal-title":"Signal Transduction Targeted Ther"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.21037\/jtd-2025-1550","article-title":"Association of systemic inflammatory markers and tertiary lymphoid structures with pathological complete response in patients with advanced lung adenocarcinoma receiving preoperative treatment: a retrospective cohort study","volume":"17","author":"Ma","year":"2025","journal-title":"J Thorac Dis"},{"key":"B19","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1038\/s43018-021-00234-4","article-title":"Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity","volume":"2","author":"Ho","year":"2021","journal-title":"Nat Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41467-024-55430-4","article-title":"Trigger inducible tertiary lymphoid structure formation using covalent organic frameworks for cancer immunotherapy","volume":"16","author":"Zhang","year":"2025","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.ccell.2026.03.004","article-title":"Myofibroblast programming blocks differentiation of TLS-organizing fibroblastic reticular cells in pancreatic cancer","volume":"44","author":"Kirschstein","year":"2026","journal-title":"Cancer Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-25-4402","article-title":"FAP-targeted LT\u03b2R agonist drives HEV differentiation and immune niche formation for improved immunotherapy response in solid tumors","volume":"32","author":"Bianchi","year":"2026","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2026.103333","article-title":"Biomimetic delivery of a STING agonist via tumor antigen-primed dendritic cell membrane nanovesicles for bladder cancer immunotherapy","volume":"39","author":"Zhang","year":"2026","journal-title":"Mater Today Bio"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2026.117009","article-title":"FAK inhibition in ovarian cancer releases omega-3 fatty acids to program CXCL13-producing anti-tumor resident peritoneal macrophages","volume":"45","author":"Chen","year":"2026","journal-title":"Cell Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2026-014914","article-title":"FLT3L-secreting cDC1 in situ vaccination enhances antitumor immunity and synergizes with PD-1 blockade in murine non-small cell lung cancer","volume":"14","author":"Abascal","year":"2026","journal-title":"J Immunother Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"5681","DOI":"10.1038\/s41467-026-74782-7","article-title":"Anti-PD-1 plus anti-CTLA-4 blockade overcomes immune exclusion in NSCLC brain metastases by enhancing CD8+ T cell responses and promoting tertiary lymphoid structure formation","volume":"17","author":"Hosoya","year":"2026","journal-title":"Nat Commun"},{"key":"B27","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.ccell.2025.12.011","article-title":"B cells disrupt tertiary lymphoid structure formation and suppress anti-tumor immunity","volume":"44","author":"Chen","year":"2026","journal-title":"Cancer Cell"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nri3700","article-title":"Ectopic lymphoid-like structures in infection, cancer and autoimmunity","volume":"14","author":"Pitzalis","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.0284","article-title":"Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures","volume":"26","author":"Dieu-Nosjean","year":"2008","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.ajpath.2011.03.007","article-title":"Unique ectopic lymph node-like structures present in human primary colorectal carcinoma are identified by immune gene array profiling","volume":"179","author":"Coppola","year":"2011","journal-title":"Am J Pathol"},{"key":"B31","doi-asserted-by":"publisher","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","year":"2018","journal-title":"Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0144-6","article-title":"Tertiary lymphoid structures in the era of cancer immunotherapy","volume":"19","author":"Saut\u00e8s-Fridman","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1186\/s40001-025-03556-6","article-title":"Tertiary lymphoid structures are associated with lower axillary residual nodal burden in breast cancer patients after neoadjuvant chemotherapy","volume":"30","author":"Wei","year":"2025","journal-title":"Eur J Med Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-25-3315","article-title":"Decoding B-cell signatures of complete pathologic response to perioperative chemoimmunotherapy in non-small cell lung cancer","volume":"32","author":"Sierra-Rodero","year":"2026","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-2025-477","article-title":"mTLS status predicts survival benefit from adjuvant chemotherapy in gastric cancer patients treated with neoadjuvant therapy and surgery","volume":"16","author":"Liu","year":"2025","journal-title":"J Gastrointestinal Oncol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1797753","article-title":"AI-driven spatial analysis of tumor-infiltrating lymphocytes predicts chemo-immunotherapy response in triple-negative breast cancer","volume":"17","author":"Liang","year":"2026","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1177\/17588359261424663","article-title":"Stromal tumor-associated eosinophils predict therapeutic resistance and survival in locally advanced tongue squamous cell carcinoma after neoadjuvant therapy","volume":"18","author":"Huang","year":"2026","journal-title":"Ther Adv Med Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jshs.2025.101063","article-title":"Prehabilitation during neoadjuvant chemotherapy results in an enhanced immune response in esophageal adenocarcinoma tumors: a randomized controlled trial","volume":"14","author":"Rayner","year":"2025","journal-title":"J Sport Health Sci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"3968","DOI":"10.1038\/s41467-025-59004-w","article-title":"Efficacy, safety and single-cell analysis of neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma: a phase II trial","volume":"16","author":"Xiang","year":"2025","journal-title":"Nat Commun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1422206","article-title":"Exploring the impact of tertiary lymphoid structures maturity in NSCLC: insights from TLS scoring","volume":"15","author":"Berthe","year":"2024","journal-title":"Front Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s00262-025-03952-1","article-title":"Distinct maturity and spatial distribution of tertiary lymphoid structures in head and neck squamous cell carcinoma: implications for tumor immunity and clinical outcomes","volume":"74","author":"Xu","year":"2025","journal-title":"Cancer Immunology Immunotherapy CII"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01992-w","article-title":"Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma","volume":"25","author":"Shu","year":"2024","journal-title":"Nat Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1606499","article-title":"Heterogeneity and distribution characteristics of tertiary lymphoid structures predict prognostic outcome in esophageal squamous cell carcinoma","volume":"16","author":"Zhang","year":"2025","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1186\/s12967-026-07950-4","article-title":"Spatial distribution analysis of tertiary lymphoid structures in esophageal squamous cell carcinoma predicts patient survival and response to neoadjuvant chemo-immunotherapy","volume":"24","author":"Wang","year":"2026","journal-title":"J Transl Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2025.2466308","article-title":"Spatial characterization of tertiary lymphoid structures as predictive biomarkers for immune checkpoint blockade in head and neck squamous cell carcinoma","volume":"14","author":"Ruiz-Torres","year":"2025","journal-title":"Oncoimmunology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.101934","article-title":"Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures","volume":"6","author":"Peyraud","year":"2025","journal-title":"Cell Rep Med"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-025-01052-x","article-title":"Spatial distribution of tertiary lymphoid structures in the molecular and clinical context of non-small cell lung cancer","volume":"48","author":"Elfving","year":"2025","journal-title":"Cell Oncol (Dordrecht Netherlands)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"},{"key":"B49","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/s41698-025-01071-9","article-title":"Intratumoral plasma cells predict patient prognosis and responsiveness to neoadjuvant immunotherapy in advanced gastric cancer","volume":"9","author":"Wang","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.cir-25-0758","article-title":"Intratumoral tertiary lymphoid structures characterized by a B cell-related signature elicit antitumor effect through HAPLN3 in hepatocellular carcinoma","volume":"14","author":"Zeng","year":"2026","journal-title":"Cancer Immunol Res"},{"key":"B51","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41591-022-02189-0","article-title":"Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial","volume":"29","author":"Cascone","year":"2023","journal-title":"Nat Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-23-0436","article-title":"Neoadjuvant durvalumab alone or combined with novel immuno-oncology agents in resectable lung cancer: the phase II NeoCOAST platform trial","volume":"13","author":"Cascone","year":"2023","journal-title":"Cancer Discov"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s568933","article-title":"A grading system of intratumoral tertiary lymphoid structure for combined hepatocellular-cholangiocarcinoma: a multicenter pathological study","volume":"12","author":"Wang","year":"2025","journal-title":"J Hepatocellular Carcinoma"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.2147\/jhc.s551462","article-title":"An interpretable radiomics-based model using susceptibility-weighted imaging for non-invasive prediction of tertiary lymphoid structures in hepatocellular carcinoma","volume":"12","author":"Liu","year":"2025","journal-title":"J Hepatocellular Carcinoma"},{"key":"B55","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41698-025-01012-6","article-title":"Machine learning model for predicting tertiary lymphoid structures and treatment response in triple-negative breast cancer","volume":"9","author":"Lin","year":"2025","journal-title":"NPJ Precis Oncol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000042566","article-title":"Predictive power of tertiary lymphoid structure for prognosis and neoadjuvant chemotherapy response in HER2-positive breast cancer","volume":"104","author":"Li","year":"2025","journal-title":"Medicine"},{"key":"B57","doi-asserted-by":"publisher","first-page":"25","DOI":"10.32604\/or.2026.077808","article-title":"Germinal center-like tertiary lymphoid structures mark immune responsiveness and enable checkpoint immunotherapy in bladder cancer","volume":"34","author":"Yin","year":"2026","journal-title":"Oncol Res"},{"key":"B58","doi-asserted-by":"publisher","first-page":"8673","DOI":"10.1038\/s41467-025-63696-5","article-title":"Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy","volume":"16","author":"Schmid","year":"2025","journal-title":"Nat Commun"},{"key":"B59","doi-asserted-by":"publisher","first-page":"399","DOI":"10.4143\/crt.2016.215","article-title":"Predictive value of tertiary lymphoid structures assessed by high endothelial venule counts in the neoadjuvant setting of triple-negative breast cancer","volume":"49","author":"Song","year":"2017","journal-title":"Cancer Res Treat"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2025.2528109","article-title":"Mature tertiary lymphoid structures linked to HPV status and anti-PD-1 based chemoimmunotherapy response in head and neck squamous cell carcinoma","volume":"14","author":"Zhang","year":"2025","journal-title":"Oncoimmunology"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102200","article-title":"Interferon-responsive HEVs drive tumor tertiary lymphoid structure formation and predict immunotherapy response in nasopharyngeal carcinoma","volume":"6","author":"Liu","year":"2025","journal-title":"Cell Rep Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/imm.70027","article-title":"Tertiary lymphoid structures predict prognosis and immune checkpoint inhibitor efficacy in lung squamous cell carcinoma","volume":"177","author":"Chen","year":"2026","journal-title":"Immunology"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000002568","article-title":"Tertiary lymphoid structures signature predicts prognosis and clinical benefits from neoadjuvant chemotherapy and PD-1 blockade in colorectal adenocarcinoma","volume":"111","author":"Guo","year":"2025","journal-title":"Int J Surg (London England)"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03324-9","article-title":"Oncolytic immunotherapy with nivolumab in muscle-invasive bladder cancer: a phase 1b trial","volume":"31","author":"Li","year":"2025","journal-title":"Nat Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2026.101020","article-title":"Immune-related pathological features and predictive score in intrahepatic cholangiocarcinoma treated with combined conversion immunotherapy","volume":"39","author":"Chen","year":"2026","journal-title":"Modern Pathol Off J United States Can Acad Pathology Inc"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-024-03123-z","article-title":"Spatial proteomic profiling elucidates immune determinants of neoadjuvant chemo-immunotherapy in esophageal squamous cell carcinoma","volume":"43","author":"Wu","year":"2024","journal-title":"Oncogene"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-013526","article-title":"Pretreatment intratumoral mature TLSs in non-clear cell renal cell carcinoma are associated with response to immunotherapy rechallenge","volume":"14","author":"Tang","year":"2026","journal-title":"J Immunother Cancer"},{"key":"B68","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41392-026-02746-w","article-title":"Neoadjuvant tislelizumab (anti-PD-1 antibody) plus chemotherapy in patients with advanced epithelial ovarian cancer: the exploratory NAIVE trial","volume":"11","author":"Zhang","year":"2026","journal-title":"Signal Transduction Targeted Ther"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02598-7","article-title":"Synergistic induction of tertiary lymphoid structures by chemoimmunotherapy in bladder cancer","volume":"130","author":"Zhang","year":"2024","journal-title":"Br J Cancer"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.21037\/tlcr-2025-17","article-title":"Tumor immune microenvironment analysis in different pathologic responses to neoadjuvant immunotherapy combined with chemotherapy in non-small cell lung cancer","volume":"14","author":"Wang","year":"2025","journal-title":"Trans Lung Cancer Res"},{"key":"B71","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1186\/s12916-026-04758-3","article-title":"Neoadjuvant camrelizumab combined with metronomic chemotherapy in patients with advanced esophageal squamous cell carcinoma: a pilot randomized phase 2 trial","volume":"24","author":"Chen","year":"2026","journal-title":"BMC Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2025.106030","article-title":"Mature tertiary lymphoid structures support B cell-mediated antitumour immunity and are disrupted by neoadjuvant therapy in rectal cancer: a multicentre, retrospective study","volume":"122","author":"Tian","year":"2025","journal-title":"EBioMedicine"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-24-1594","article-title":"Chemotherapy drives tertiary lymphoid structures that correlate with ICI-responsive TCF1+CD8+ T cells in metastatic ovarian cancer","volume":"31","author":"Lanickova","year":"2025","journal-title":"Clin Cancer Res Off J Am Assoc For Cancer Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202514332","article-title":"T cell exhaustion and dendritic cell-mediated tertiary lymphoid structures (TLSs) modulation affect response to neoadjuvant chemoradiotherapy in microsatellite stable rectal cancer","volume":"13","author":"Wang","year":"2026","journal-title":"Advanced Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.955187","article-title":"Identification of four immune subtypes in locally advanced rectal cancer treated with neoadjuvant chemotherapy for predicting the efficacy of subsequent immune checkpoint blockade","volume":"13","author":"He","year":"2022","journal-title":"Front Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1378190","article-title":"Neoadjuvant chemotherapy is associated with suppression of the B cell-centered immune landscape in pancreatic ductal adenocarcinoma","volume":"15","author":"Rupp","year":"2024","journal-title":"Front Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1663396","article-title":"Characteristics of tertiary lymphoid structures in prostate cancer and the impact of neoadjuvant therapy on their formation and maturation","volume":"16","author":"Liu","year":"2025","journal-title":"Front Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.cir-25-0387","article-title":"Neoadjuvant immunotherapy promotes the formation of mature tertiary lymphoid structures in a remodeled pancreatic tumor microenvironment","volume":"13","author":"Sidiropoulos","year":"2025","journal-title":"Cancer Immunol Res"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009762","article-title":"Perioperative chemoimmunotherapy induces strong immune responses and long-term survival in patients with HLA class I-deficient non-small cell lung cancer","volume":"12","author":"Molina-Alejandre","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1579840","article-title":"The germinal center-tertiary lymphoid structure after neoadjuvant chemo-immunotherapy for locally advanced lung squamous cell carcinoma can predict the disease progression","volume":"16","author":"Jiang","year":"2025","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1244256","article-title":"Combined inflammatory parameters and tertiary lymphoid structure predict prognosis in patients with resectable non-small cell lung cancer treated with neoadjuvant chemoimmunotherapy","volume":"14","author":"Xu","year":"2023","journal-title":"Front Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2024.217178","article-title":"Survival benefit and spatial properties of tertiary lymphoid structures in esophageal squamous cell carcinoma with neoadjuvant therapies","volume":"601","author":"Huang","year":"2024","journal-title":"Cancer Lett"},{"key":"B83","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12957-025-03796-0","article-title":"Correlation analysis of tertiary lymphoid structure parameters with the prognosis of patients with locally advanced rectal cancer after neoadjuvant chemotherapy: a retrospective study","volume":"23","author":"Jiang","year":"2025","journal-title":"World J Surg Oncol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1616247","article-title":"Tertiary lymphoid structures correlate with the therapeutic efficacy and prognosis of resectable esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiotherapy plus immunotherapy","volume":"16","author":"Zhai","year":"2025","journal-title":"Front Immunol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40164-026-00748-6","article-title":"Tertiary lymphoid structures correlate with reduced recurrence risk and enhanced antitumor immunity in esophageal squamous cell carcinoma with pathologic non-complete response to neoadjuvant chemoimmunotherapy","volume":"15","author":"Wo","year":"2026","journal-title":"Exp Hematol Oncol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1740643","article-title":"A multimodal biological margin risk index predicts recurrence after neoadjuvant immunochemotherapy in head and neck squamous cell carcinoma","volume":"17","author":"Xu","year":"2026","journal-title":"Front Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2026.101004","article-title":"Mature tertiary lymphoid structures in breast cancers are associated with antitumor immunity and better prognosis","volume":"39","author":"Yu","year":"2026","journal-title":"Modern Pathol Off J United States Can Acad Pathology Inc"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17203351","article-title":"Tertiary lymphoid structures are associated with favorable clinical outcomes and negatively correlated with cancer-associated fibroblasts in esophageal cancer","volume":"17","author":"Kunitomo","year":"2025","journal-title":"Cancers"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2023.2285902","article-title":"Complete pathological remission and tertiary lymphoid structures are associated with the efficacy of resectable NSCLC receiving neoadjuvant chemoimmunotherapy: a double-center retrospective study","volume":"19","author":"Liu","year":"2023","journal-title":"Hum Vaccines Immunotherapeutics"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70228","article-title":"The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: a retrospective study","volume":"13","author":"Wang","year":"2024","journal-title":"Cancer Med"},{"key":"B91","doi-asserted-by":"publisher","first-page":"174","DOI":"10.21037\/tlcr-2026-1-0050","article-title":"The impact of local tumor immune responses on prognosis in resected lung adenocarcinoma","volume":"15","author":"Ichiki","year":"2026","journal-title":"Trans Lung Cancer Res"},{"key":"B92","doi-asserted-by":"publisher","first-page":"4552","DOI":"10.1038\/s41467-026-71161-0","article-title":"The CD4+ T cell population partners with Tpex CD8+ T cells to mediate antitumor immunity in the tumor microenvironment","volume":"17","author":"Takei","year":"2026","journal-title":"Nat Commun"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1093\/discim\/kyag007","article-title":"CCR2- T peripheral helper cells as potential coordinators of local immune architecture in human cancer","volume":"5","author":"Crespo Oliva","year":"2026","journal-title":"Discov Immunol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12943-025-02287-w","article-title":"Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer","volume":"24","author":"Cui","year":"2025","journal-title":"Mol Cancer"},{"key":"B95","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s12885-025-15529-3","article-title":"High endothelial venules abundance in tertiary lymphoid structures: a prognostic biomarker in non-small cell lung cancer with neoadjuvant immunochemotherapy","volume":"26","author":"Zhang","year":"2026","journal-title":"BMC Cancer"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6020969","article-title":"Role of tertiary lymphoid structures (TLS) in anti-tumor immunity: potential tumor-induced cytokines\/chemokines that regulate TLS formation in epithelial-derived cancers","volume":"6","author":"Pimenta","year":"2014","journal-title":"Cancers"},{"key":"B97","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/bs.acr.2015.05.001","article-title":"Control of CD8 T-cell infiltration into tumors by vasculature and microenvironment","volume":"128","author":"Peske","year":"2015","journal-title":"Adv Cancer Res"},{"key":"B98","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1007\/s00262-025-04265-z","article-title":"Tumor-associated high endothelial venules are associated with enhanced lymphocyte infiltration and favorable prognosis in resected hepatocellular carcinoma","volume":"75","author":"Aoyama","year":"2025","journal-title":"Cancer Immunology Immunotherapy CII"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1009306","article-title":"Tumor necrosis factor receptor regulation of peripheral node addressin biosynthetic components in tumor endothelial cells","volume":"13","author":"Rodriguez","year":"2022","journal-title":"Front Immunol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2023.100705","article-title":"Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer","volume":"36","author":"Ruddle","year":"2023","journal-title":"Curr Opin Physiol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41392-026-02858-3","article-title":"Tumor-draining lymph nodes shape the tumor microenvironment through enrichment of tumor-reactive effector-exhausted CD8+ T cells","volume":"11","author":"Kong","year":"2026","journal-title":"Signal Transduction Targeted Ther"},{"key":"B102","doi-asserted-by":"publisher","first-page":"4228","DOI":"10.1038\/s41467-025-59341-w","article-title":"Mature tertiary lymphoid structures evoke intra-tumoral T and B cell responses via progenitor exhausted CD4+ T cells in head and neck cancer","volume":"16","author":"Li","year":"2025","journal-title":"Nat Commun"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-012224","article-title":"Tertiary lymphoid structures in Merkel cell carcinoma facilitate na\u00efve and central memory T-cell infiltration linked to immunotherapy response","volume":"13","author":"Srinivas","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00067","article-title":"Tertiary lymphoid structure-associated B cells are key players in anti-tumor immunity","volume":"6","author":"Germain","year":"2015","journal-title":"Front Immunol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1172\/jci67428","article-title":"CD4+ follicular helper T cell infiltration predicts breast cancer survival","volume":"123","author":"Gu-Trantien","year":"2013","journal-title":"J Clin Invest"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2021.1900635","article-title":"Germinal center reactions in tertiary lymphoid structures associate with neoantigen burden, humoral immunity and long-term survivorship in pancreatic cancer","volume":"10","author":"Gunderson","year":"2021","journal-title":"Oncoimmunology"},{"key":"B107","doi-asserted-by":"publisher","first-page":"3349","DOI":"10.1038\/s41467-021-23355-x","article-title":"B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma","volume":"12","author":"Ruffin","year":"2021","journal-title":"Nat Commun"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.793964","article-title":"The tumor immune landscape and architecture of tertiary lymphoid structures in urothelial cancer","volume":"12","author":"van Dijk","year":"2021","journal-title":"Front Immunol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1126\/science.ady1678","article-title":"Dendritic cells control tertiary lymphoid structure development and maintenance in cancer","volume":"393","author":"Mattiuz","year":"2026","journal-title":"Science"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.006","article-title":"Regulatory T cells in tumor-associated tertiary lymphoid structures suppress anti-tumor T cell responses","volume":"43","author":"Joshi","year":"2015","journal-title":"Immunity"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2024.05.009","article-title":"CCL9\/CCR1 axis-driven chemotactic nanovesicles for attenuating metastasis of SMAD4-deficient colorectal cancer by trapping TGF-\u03b2","volume":"14","author":"Niu","year":"2024","journal-title":"Acta Pharm Sin B"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2026.03.022","article-title":"The phosphatase DUSP2 constrains lymphoid remodeling and immunotherapy response in lung squamous carcinoma","volume":"34","author":"Wang","year":"2026","journal-title":"Mol Ther J Am Soc Gene Ther"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011882","article-title":"Multiomics elucidation of surrounding AT2 cells impeding tertiary lymphoid structures function in neoadjuvant chemoimmunotherapy response of multiple primary lung cancers","volume":"13","author":"Wang","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.7150\/thno.118269","article-title":"MIF-expressing tumor cells mediate immunotherapeutic resistance in esophageal squamous cell carcinoma","volume":"16","author":"Song","year":"2026","journal-title":"Theranostics"},{"key":"B115","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12935-025-04161-7","article-title":"Single-cell spatial analysis identifies ID1-high endothelial cells in tertiary lymphoid structures as predictors of durable response to immunotherapy in non-small cell lung cancer","volume":"26","author":"Matsumoto","year":"2026","journal-title":"Cancer Cell Int"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02259-8","article-title":"Simultaneous STING and lymphotoxin-\u03b2 receptor activation induces B cell responses in tertiary lymphoid structures to potentiate antitumor immunity","volume":"26","author":"Sawada","year":"2025","journal-title":"Nat Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2019.1583547","article-title":"APC germline hepatoblastomas demonstrate cisplatin-induced intratumor tertiary lymphoid structures","volume":"8","author":"Morcrette","year":"2019","journal-title":"Oncoimmunology"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001136","article-title":"CXCL13 shapes immunoactive tumor microenvironment and enhances the efficacy of PD-1 checkpoint blockade in high-grade serous ovarian cancer","volume":"9","author":"Yang","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001906","article-title":"STING agonist-based treatment promotes vascular normalization and tertiary lymphoid structure formation in the therapeutic melanoma microenvironment","volume":"9","author":"Chelvanambi","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109422","article-title":"Immune mechanisms orchestrate tertiary lymphoid structures in tumors via cancer-associated fibroblasts","volume":"36","author":"Rodriguez","year":"2021","journal-title":"Cell Rep"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1002\/advs.75790","article-title":"SSR4 sustains tertiary lymphoid structures by regulation quality control of N-linked glycosylation during B-cell differentiation into plasmacyte in colorectal cancer","volume":"13","author":"Zhao","year":"2026","journal-title":"Advanced Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2026.106280","article-title":"TCF1+CD4+ T cells and microglia co-orchestrate tertiary lymphoid structures to enhance prognosis and immunotherapy in non-small cell lung cancer with brain metastases","volume":"127","author":"Yu","year":"2026","journal-title":"EBioMedicine"},{"key":"B123","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1186\/s12967-020-02370-4","article-title":"Neoadjuvant rituximab modulates the tumor immune environment in patients with high risk prostate cancer","volume":"18","author":"Ryan","year":"2020","journal-title":"J Transl Med"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-012121","article-title":"Memory B cell subset shapes antitumor immunity and response to PD-1 blockade in mismatch repair-deficient colorectal cancers","volume":"14","author":"Huang","year":"2026","journal-title":"J Immunother Cancer"},{"key":"B125","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/cncy.20147","article-title":"Biospecimen reporting for improved study quality (BRISQ)","volume":"119","author":"Moore","year":"2011","journal-title":"Cancer Cytopathol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dji237","article-title":"Reporting recommendations for tumor marker prognostic studies (REMARK)","volume":"97","author":"McShane","year":"2005","journal-title":"J Natl Cancer Institute"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1948933\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:21:12Z","timestamp":1789032072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1948933\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":126,"alternative-id":["10.3389\/fimmu.2026.1948933"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1948933","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"article-number":"1948933"}}