{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:03:01Z","timestamp":1791198181023,"version":"4.1.0"},"reference-count":79,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tertiary lymphoid structures (TLSs) have emerged as clinically relevant immune niches associated with improved survival and enhanced response to immune checkpoint inhibitors across multiple solid tumors. However, translational evaluation remains dominated by density-based scoring, which inadequately captures the functional heterogeneity of histologically similar lymphoid aggregates. This review synthesizes recent advances in spatial biology that support a shift from counting TLSs to interpreting them as spatially organized immune microenvironmental units embedded within local tumor ecosystems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>Evidence from spatial transcriptomics, multiplexed imaging, single-cell profiling, computational pathology, and spatial-proteomic approaches converges on four coupled requirements for productive TLS function: stromal licensing through lymphotoxin-dependent chemokine circuits, vascular competence mediated by specialized high endothelial venules, helper T-cell programs that bridge follicular and cytotoxic immunity, and a permissive metabolic context that enables maturation. Spatial studies further show that regulatory infiltration, suppressive plasma-cell programs, and metabolic disruption can decouple structural presence from effective antitumor immunity. Across tumor types, these insights indicate that biomarker performance improves when TLS density is integrated with maturity, anatomical location, HEV coupling, immune composition, and treatment context rather than used as a standalone metric. We further discuss how spatial analyses reveal actionable pathways for inducing or reprogramming TLSs and outline a staged, module-matched composite biomarker workflow combining digital pathology, targeted multiplexed imaging, and focused molecular or metabolic augmentation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TLSs should be regarded as spatially organized, functionally heterogeneous immune microenvironmental units rather than biologically equivalent lymphoid aggregates. A spatial-functional framework helps explain productive, arrested, and suppressive TLS states, provides a basis for next-generation composite biomarkers, and supports module-matched therapeutic strategies tailored to the stromal, vascular, helper-cell, or metabolic bottleneck limiting TLS function in individual tumors. The immediate next step is prospective validation of a minimal TLS panel across defined treatment contexts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1865949","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:32:16Z","timestamp":1791196336000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["From density to spatial function: spatial multi-omics, composite biomarker design, and therapeutic engineering of tertiary lymphoid structures in solid tumors"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuchen","family":"Wang","sequence":"first","affiliation":[{"name":"The Sixth Clinical Medical College of Guangzhou Medical University (Qingyuan People\u2019s Hospital)","place":["Qingyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of Shenzhen University, The Second People\u2019s Hospital of Shenzhen","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"B1","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"},{"key":"B2","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":"B3","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":"B4","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":"B5","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":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1906-8","article-title":"B cells are associated with survival and immunotherapy response in sarcoma","volume":"577","author":"Petitprez","year":"2020","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.08.009","article-title":"Tertiary lymphoid structures and B cells: an intratumoral immunity cycle","volume":"56","author":"Fridman","year":"2023","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1267654","article-title":"Mechanisms of tertiary lymphoid structure formation: cooperation between inflammation and antigenicity","volume":"14","author":"Khanal","year":"2023","journal-title":"Front Immunol"},{"key":"B9","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":"B10","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":"Hernandez-Verdin","year":"2026","journal-title":"J Exp Clin Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"7713","DOI":"10.1038\/s41467-024-52153-4","article-title":"Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma","volume":"15","author":"Liu","year":"2024","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.ccell.2025.03.011","article-title":"Spatial transcriptomics reveals tryptophan metabolism restricting maturation of intratumoral tertiary lymphoid structures","volume":"43","author":"Tang","year":"2025","journal-title":"Cancer Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1342","article-title":"Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells","volume":"74","author":"Goc","year":"2014","journal-title":"Cancer Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201309-1611OC","article-title":"Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer","volume":"189","author":"Germain","year":"2014","journal-title":"Am J Respir Crit Care Med"},{"key":"B15","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 (Dordr)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2153911","article-title":"High endothelial venules proportion in tertiary lymphoid structure is a prognostic marker and correlated with anti-tumor immune microenvironment in colorectal cancer","volume":"55","author":"Zhan","year":"2023","journal-title":"Ann Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-025-04268-w","article-title":"Multi-omics profiling reveals an immunosuppressive plasma cell subset within tertiary lymphoid structures in cervical cancer","volume":"75","author":"Huang","year":"2026","journal-title":"Cancer Immunol Immunother"},{"key":"B18","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":"B19","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1038\/s42003-022-04356-y","article-title":"Regulatory T cells infiltrate the tumor-induced tertiary lymphoid structures and are associated with poor clinical outcome in NSCLC","volume":"5","author":"Devi-Marulkar","year":"2022","journal-title":"Commun Biol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s13046-025-03318-6","article-title":"Multiple mechanisms and applications of tertiary lymphoid structures and immune checkpoint blockade","volume":"44","author":"Li","year":"2025","journal-title":"J Exp Clin Cancer Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/j.cell.2020.07.005","article-title":"Coordinated cellular neighborhoods orchestrate antitumoral immunity at the colorectal cancer invasive front","volume":"182","author":"Sch\u00fcrch","year":"2020","journal-title":"Cell"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3836","article-title":"De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors","volume":"18","author":"Johansson-Percival","year":"2017","journal-title":"Nat Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1414884","article-title":"Associations between tertiary lymphoid structure density and immune checkpoint inhibitor efficacy in solid tumors: systematic review and meta-analysis","volume":"15","author":"Jiang","year":"2024","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1126\/science.aaf2403","article-title":"Visualization and analysis of gene expression in tissue sections by spatial transcriptomics","volume":"353","author":"St\u00e5hl","year":"2016","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw1219","article-title":"Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution","volume":"363","author":"Rodriques","year":"2019","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0739-1","article-title":"Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2","volume":"39","author":"Stickels","year":"2021","journal-title":"Nat Biotechnol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02040-9","article-title":"Advances in spatial transcriptomics and its applications in cancer research","volume":"23","author":"Jin","year":"2024","journal-title":"Mol Cancer"},{"key":"B28","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s13045-024-01596-9","article-title":"Spatial multi-omics: deciphering technological landscape of integration of multi-omics and its applications","volume":"17","author":"Liu","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02882-6","article-title":"Spatial analysis by current multiplexed imaging technologies for the molecular characterisation of cancer tissues","volume":"131","author":"Semba","year":"2024","journal-title":"Br J Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1016\/j.cell.2022.04.003","article-title":"Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays","volume":"185","author":"Chen","year":"2022","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-025-02193-3","article-title":"High-definition spatial transcriptomic profiling of immune cell populations in colorectal cancer","volume":"57","author":"Oliveira","year":"2025","journal-title":"Nat Genet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10435","DOI":"10.1038\/s41467-025-65421-8","article-title":"Single-cell and spatial transcriptomics implicate a prognostic function of tertiary lymphoid structures in gastric cancer","volume":"16","author":"Wang","year":"2025","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2025.116250","article-title":"Integrated spatial transcriptomic profiling to dissect the cellular characteristics of tumor-associated tertiary lymphoid structures","volume":"44","author":"Li","year":"2025","journal-title":"Cell Rep"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3488","article-title":"Multiplexed ion beam imaging of human breast tumors","volume":"20","author":"Angelo","year":"2014","journal-title":"Nat Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.cell.2018.07.010","article-title":"Deep profiling of mouse splenic architecture with CODEX multiplexed imaging","volume":"174","author":"Goltsev","year":"2018","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1383932","article-title":"Unveiling spatial complexity in solid tumor immune microenvironments through multiplexed imaging","volume":"15","author":"Scheuermann","year":"2024","journal-title":"Front Immunol"},{"key":"B37","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":"B38","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":"B39","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1016\/j.ccell.2024.09.007","article-title":"The activity of tertiary lymphoid structures in high grade serous ovarian cancer is governed by site, stroma, and cellular interactions","volume":"42","author":"MacFawn","year":"2024","journal-title":"Cancer Cell"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adh1315","article-title":"Dysfunctional CD11c-CD21- extrafollicular memory B cells are enriched in the periphery and tumors of patients with cancer","volume":"17","author":"Ruffin","year":"2025","journal-title":"Sci Transl Med"},{"key":"B41","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":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s43856-023-00421-7","article-title":"Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors","volume":"4","author":"van Rijthoven","year":"2024","journal-title":"Commun Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-4184-2_12","article-title":"Cancer-associated lymphoid aggregates in histology images: manual and deep learning-based quantification approaches","volume":"2864","author":"Silina","year":"2025","journal-title":"Methods Mol Biol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"9845","DOI":"10.1038\/s41598-025-94664-0","article-title":"Automated classification of tertiary lymphoid structures in colorectal cancer using TLS-PAT artificial intelligence tool","volume":"15","author":"Le Rochais","year":"2025","journal-title":"Sci Rep"},{"key":"B45","doi-asserted-by":"publisher","first-page":"34","DOI":"10.36922\/TD025250049","article-title":"Structural cell communities in the tumor microenvironment: Spatial determinants of therapeutic response","volume":"4","author":"Cui","year":"2025","journal-title":"Tumor Discov"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120252","article-title":"Stromal cells in chronic inflammation and tertiary lymphoid organ formation","volume":"33","author":"Buckley","year":"2015","journal-title":"Annu Rev Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00477","article-title":"Stromal fibroblasts in tertiary lymphoid structures: a novel target in chronic inflammation","volume":"7","author":"Barone","year":"2016","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002101","article-title":"PD-1+CXCR5-CD4+ Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma","volume":"9","author":"Li","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1002\/mc.70058","article-title":"Single-cell and spatial transcriptomic analysis reveals shared and cancer-type-specific cellular interactions and chemokine signaling associated with tertiary lymphoid structures in colorectal and gastric cancers","volume":"65","author":"Wang","year":"2026","journal-title":"Mol Carcinog"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08426-5","article-title":"IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer","volume":"638","author":"Amisaki","year":"2025","journal-title":"Nature"},{"key":"B51","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41392-025-02260-5","article-title":"De novo induction of tertiary lymphoid structures: an immunotherapeutic strategy in pancreatic cancer","volume":"10","author":"Ahmed","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00491","article-title":"High endothelial venules and lymphatic vessels in tertiary lymphoid organs: characteristics, functions, and regulation","volume":"7","author":"Ruddle","year":"2016","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.736670","article-title":"High endothelial venules: a vascular perspective on tertiary lymphoid structures in cancer","volume":"12","author":"Vella","year":"2021","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.002","article-title":"High endothelial venules in cancer: regulation, function, and therapeutic implication","volume":"41","author":"Vella","year":"2023","journal-title":"Cancer Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1038\/s41467-022-29701-x","article-title":"Loss of vascular endothelial Notch signaling promotes spontaneous formation of tertiary lymphoid structures","volume":"13","author":"Fleig","year":"2022","journal-title":"Nat Commun"},{"key":"B56","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":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-026-10808-w","article-title":"Tertiary lymphoid structures harbour stem-like tumour-specific T cells","volume":"656","author":"Afeyan","year":"2026","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009603","article-title":"Intratumoral CXCL13+CD160+CD8+ T cells promote the formation of tertiary lymphoid structures to enhance the efficacy of immunotherapy in advanced gastric cancer","volume":"12","author":"Wang","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.865596","article-title":"CD20+CD22+ADAM28+ B cells in tertiary lymphoid structures promote immunotherapy response","volume":"13","author":"Wu","year":"2022","journal-title":"Front Immunol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.1038\/s41467-021-24347-7","article-title":"Agonistic CD40 therapy induces tertiary lymphoid structures but impairs responses to checkpoint blockade in glioma","volume":"12","author":"van Hooren","year":"2021","journal-title":"Nat Commun"},{"key":"B61","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1186\/s12885-024-12587-x","article-title":"Prognostic and clinicopathological significance of tertiary lymphoid structure in non-small cell lung cancer: a systematic review and meta-analysis","volume":"24","author":"Ma","year":"2024","journal-title":"BMC Cancer"},{"key":"B62","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":"B63","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00262-025-04165-2","article-title":"Tertiary lymphoid structures gene signature predicts response to immunotherapy plus chemotherapy in advanced non-small cell lung cancer","volume":"74","author":"Du","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-002273","article-title":"Heterogeneity in tertiary lymphoid structure B-cells correlates with patient survival in metastatic melanoma","volume":"9","author":"Lynch","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102821","article-title":"Existence of intratumoral tertiary lymphoid structures is associated with immune cells infiltration and predicts better prognosis in early-stage hepatocellular carcinoma","volume":"12","author":"Li","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B66","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41698-024-00533-w","article-title":"Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer","volume":"8","author":"Wang","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-24-0979","article-title":"Tertiary lymphoid structures are associated with enhanced macrophage activation and immune checkpoint expression, and predict outcome in cervical cancer","volume":"13","author":"Gorvel","year":"2025","journal-title":"Cancer Immunol Res"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1473969","article-title":"Tertiary lymphoid structures: exploring opportunities to improve immunotherapy in ovarian cancer","volume":"16","author":"Varghese","year":"2025","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200913","article-title":"Activation of 4-1BBL+ B cells with CD40 agonism and IFN\u03b3 elicits potent immunity against glioblastoma","volume":"218","author":"Lee-Chang","year":"2021","journal-title":"J Exp Med"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1126\/science.adz2742","article-title":"Pan-cancer spatial atlas of tertiary lymphoid structures","volume":"392","author":"Cho","year":"2026","journal-title":"Science"},{"key":"B71","doi-asserted-by":"publisher","first-page":"100546","DOI":"10.1016\/j.medj.2024.10.023","article-title":"Tertiary lymphoid structures and cancer immunotherapy: from bench to bedside","volume":"6","author":"Peyraud","year":"2025","journal-title":"Med"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01821-3","article-title":"Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort","volume":"28","author":"Italiano","year":"2022","journal-title":"Nat Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00407","article-title":"Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention","volume":"7","author":"Saut\u00e8s-Fridman","year":"2016","journal-title":"Front Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.1158\/0008-5472.CAN-23-2716","article-title":"LT\u03b2R agonism promotes antitumor immune responses via modulation of the tumor microenvironment","volume":"84","author":"An","year":"2024","journal-title":"Cancer Res"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2026.116510","article-title":"Targeting tumor-associated sympathetic nerves orchestrates tertiary lymphoid structures to enhance PD-1\/PD-L1 blockade efficacy","volume":"177","author":"Zeng","year":"2026","journal-title":"Int Immunopharmacol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2025.123976","article-title":"Self-assembled microparticle hydrogel scaffolds to construct artificial tertiary lymphoids for enhanced CAR-T cell therapy against solid tumors","volume":"329","author":"Li","year":"2026","journal-title":"Biomaterials"},{"key":"B77","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":"B78","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.semcancer.2025.12.009","article-title":"Spatial multi-omics in precision medicine: integrating biological insights through multidisciplinary collaboration","volume":"119","author":"Kim","year":"2026","journal-title":"Semin Cancer Biol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12943-024-01980-6","article-title":"Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application","volume":"23","author":"Zhang","year":"2024","journal-title":"Mol Cancer"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1865949\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:32:17Z","timestamp":1791196337000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1865949\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":79,"alternative-id":["10.3389\/fimmu.2026.1865949"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1865949","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,5]]},"article-number":"1865949"}}