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Journal articles on the topic 'Tertiary lymphoid structure (TLS)'

Author: Grafiati

Published: 23 November 2024

Last updated: 31 July 2025

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1

Gorecki, Grace, Lan Gardner Coffman, Sarah E. Taylor, and Tullia C. Bruno. "Tertiary lymphoid structure prevalence and prognostic value in cervical cancer." Journal of Clinical Oncology 41, no. 16_suppl (2023): e17521-e17521. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e17521.

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e17521 Background: Recurrent or progressive cervical cancer have limited second-line treatment options. Response rates are often poor to second-line therapy (average response rate of 15%). Identification of factors which predict response to immunotherapy and targets to enhance the immune response are critically needed in cervical cancer. Chronic inflammation can initiate an immune response in non-secondary lymphoid organs (SLO) and form a Tertiary Lymphoid Structure (TLS). TLS is composed of immune cells clustered and organized and responsible for immune cell chemotaxis, which impacts cancer t

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Amwas, Nour, Darya Alizadeh, Christine Brown, et al. "Abstract A038: Inducing tumor associated tertiary lymphoid structures using cellular therapy." Cancer Immunology Research 13, no. 2_Supplement (2025): A038. https://doi.org/10.1158/2326-6074.io2025-a038.

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Abstract Targeting the tumor microenvironment (TME) to be more immune permissive is a potential strategy for enhancing immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy, providing a promising avenue for treating aggressive tumors such as glioblastoma multiforme (GBM). Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that arise in response to chronic inflammation and mimic the structure and function of secondary lymphoid organs. The spontaneous presence of TLS in some solid tumors, including GBM, is associated with improved clinical outcome and responsi

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Zou, Ji’an, Yingzhe Zhang, Yue Zeng, et al. "Tertiary Lymphoid Structures: A Potential Biomarker for Anti-Cancer Therapy." Cancers 14, no. 23 (2022): 5968. http://dx.doi.org/10.3390/cancers14235968.

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A tertiary lymphoid structure (TLS) is a special component in the immune microenvironment that is mainly composed of tumor-infiltrating lymphocytes (TILs), including T cells, B cells, DC cells, and high endothelial venules (HEVs). For cancer patients, evaluation of the immune microenvironment has a predictive effect on tumor biological behavior, treatment methods, and prognosis. As a result, TLSs have begun to attract the attention of researchers as a new potential biomarker. However, the composition and mechanisms of TLSs are still unclear, and clinical detection methods are still being explo

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Lynch, Kevin T., Samuel J. Young, Max O. Meneveau, et al. "Heterogeneity in tertiary lymphoid structure B-cells correlates with patient survival in metastatic melanoma." Journal for ImmunoTherapy of Cancer 9, no. 6 (2021): e002273. http://dx.doi.org/10.1136/jitc-2020-002273.

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BackgroundTertiary lymphoid structures (TLSs) are immune aggregates in peripheral tissues that may support adaptive immune responses. Their presence has been associated with clinical response to checkpoint blockade therapy (CBT), but it is unknown whether TLS have prognostic significance independent of CBT in melanoma. We hypothesized that TLS in melanoma metastases would be associated with increased intratumoral lymphocyte infiltration, but that the intra-TLS immunological milieu would be distinct from the intratumoral immunological milieu. We also hypothesized that the presence of TLS would

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Nayar, Saba, Joana Campos, Charlotte G. Smith, et al. "Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology." Proceedings of the National Academy of Sciences 116, no. 27 (2019): 13490–97. http://dx.doi.org/10.1073/pnas.1905301116.

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Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earlie

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Yu, Jinglu, Yabin Gong, Xiaowei Huang, and Yufang Bao. "Prognostic and therapeutic potential of gene profiles related to tertiary lymphoid structures in colorectal cancer." PeerJ 12 (October 31, 2024): e18401. http://dx.doi.org/10.7717/peerj.18401.

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The role of tertiary lymphoid structures (TLS) in oncology is gaining interest, particularly in colorectal carcinoma, yet a thorough analysis remains elusive. This study pioneered a novel TLS quantification system for prognostic and therapeutic response prediction in colorectal carcinoma, alongside a comprehensive depiction of the TLS landscape. Utilizing single-cell sequencing, we established a TLS score within the Tumor Immune Microenvironment (TIME). Analysis of tertiary lymphoid structure-related genes (TLSRGs) in 1,184 patients with colon adenocarcinoma/rectum adenocarcinoma (COADREAD) fr

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Boulat, Victoire, Elena Alberts, Carin Andrea Brundin, Dinis P. Calado, and Anita Grigoriadis. "Abstract 1375: Active inhibition of chemokine-mediated migration impairs tertiary lymphoid structure formation." Cancer Research 85, no. 8_Supplement_1 (2025): 1375. https://doi.org/10.1158/1538-7445.am2025-1375.

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Abstract The presence of tumor-infiltrating B cells (TIL-B) and tertiary lymphoid structures (TLS) in the primary tumor microenvironment carries prognostic value across cancer types. We have shown that triple-negative breast cancer (TNBC) patients with robust germinal center (GC) responses in their lymph nodes (LN) exhibit higher levels of TILs and more TLS. In this study, we investigated human and mouse immune-cold TNBCs to uncover mechanisms by which tumor-LN crosstalk may be impaired. In orthotopic TNBC mouse models, we observed robust GC responses in tumor-draining LNs. However, minimal TI

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Tang, Weilong, Chaiyaporn Kuwentrai, Matthew J. Webber, Zhou Ye, and Jiandong Huang. "Abstract 862: Dynamic hydrogel drug delivery systems for enhancing tertiary lymphoid structure formation and maturation." Cancer Research 85, no. 8_Supplement_1 (2025): 862. https://doi.org/10.1158/1538-7445.am2025-862.

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Introduction: Tertiary lymphoid structures (TLSs), also known as ectopic lymphoid structures, are organized lymphoid-like aggregates that can form within the tumor microenvironment. TLSs exhibit similar structural and functional characteristics to secondary lymphoid organs, such as lymph nodes, and are associated with improved cancer prognosis and enhanced immune responses, including immune checkpoint blockade (ICB) therapies. However, inducing mature TLSs remains a significant challenge. Our study aims to develop a dynamic hydrogel drug delivery system that stimulates the formation and matura

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Gonzalez, Ricardo A. Chaurio, Kyle K. Payne, Carmen Maria Anadon Galindo, et al. "Satb1 deficiency licenses TFH-differentiation and Tertiary Lymphoid Structure formation in cancer." Journal of Immunology 204, no. 1_Supplement (2020): 89.2. http://dx.doi.org/10.4049/jimmunol.204.supp.89.2.

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Abstract Tertiary Lymphoid Structures (TLS) are commonly identified in human tumors with improved outcome, but how they are orchestrated remains elusive. Here we show that silencing of the master genomic organizer Satb1 results in enhanced antigen-specific T Follicular Helper (TFH) differentiation. Increased TFH thereby promoted antigen-specific intra-tumoral CD19+B220+ B cell responses and spontaneous TLS assembly upon ovarian tumor challenge. Mechanistically, Satb1 deficiency drives increased TFH formation through de-repression of ICOS and PD-1. Accordingly, TGF-β1-driven downregulation of S

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Chung, Shin-Yi, Yi-Chen Yeh, Chien-Jung Huang, et al. "Comparative impact of tertiary lymphoid structures and tumor-infiltrating lymphocytes in cholangiocarcinoma." Journal for ImmunoTherapy of Cancer 13, no. 1 (2025): e010173. https://doi.org/10.1136/jitc-2024-010173.

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BackgroundCholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear. This study elucidates their contributions to the TME.MethodsWe examined 16 tumor samples from a single-arm, phase II trial of nivolumab plus modifie

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Thelen, M., MA García-Márquez, T. Nestler, et al. "P03.03 Organization, function and gene expression of tertiary lymphoid structures in PDAC resembles lymphoid follicles in secondary lymphoid organs." Journal for ImmunoTherapy of Cancer 8, Suppl 2 (2020): A23.1—A23. http://dx.doi.org/10.1136/jitc-2020-itoc7.43.

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BackgroundSecondary lymphoid organs (SLO) are involved in induction and enhancement of anti-tumor immune responses on different tumor entities. Recent evidence suggests that anti-tumor immune responses may also be induced or enhanced in the tumor microenvironment in so called tertiary lymphoid structures (TLS). It is assumed that TLS represent a hotspot for T cell priming, B cell activation, and differentiation, leading to cellular and humoral anti-tumor immune response.MethodsFFPE-slides of 120 primary pancreatic ductal adenocarcinoma (PDAC) patients were immunohistochemically (IHC) stained f

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Zou, Yi, Jing Zhao, Fengbo Huang, Xueping Xiang, and Yang Xia. "Decreased Tertiary Lymphoid Structures in Lung Adenocarcinomas with ALK Rearrangements." Journal of Clinical Medicine 11, no. 19 (2022): 5935. http://dx.doi.org/10.3390/jcm11195935.

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Purpose: This study sought to characterize the tumor immune microenvironment (TIME) of lung adenocarcinomas with ALK rearrangements (ALK+ LUAD), which responds poorly to immune checkpoint inhibitors (ICIs) therapy. Materials and methods: Immune score evaluation and immunohistochemical (IHC) validation of B cells, cytotoxic, helper, regulatory T cells, dendritic cells, and tumor-associated macrophages were performed on the TCGA cohort and the whole tissue sections of our matched surgical samples, respectively, between ALK+ and ALK− LUAD. The formation and spatial organization of TLS, intra- and

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Sofronii, Doïna, Francine Padonou, Mireille Langouo, et al. "Abstract 4618: Biomarkers of functionally active tertiary lymphoid structures in human breast cancer." Cancer Research 83, no. 7_Supplement (2023): 4618. http://dx.doi.org/10.1158/1538-7445.am2023-4618.

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Abstract The clinical relevance of tumor infiltrating lymphocytes (TIL) in breast cancer (BC) is now widely accepted and being implemented in clinical practice. Our lab previously demonstrated that 60% of BC organize some of their TIL in tertiary lymphoid structures (TLS). TLS have been detected in a wide variety of solid tumors with their prognostic value and importance in the response to immunotherapy increasingly accepted. Reliable biomarkers to identify and characterize TLS and their immune activities in tumors are needed. The specific aim of this project was to perform a comprehensive ana

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Luo, Ran, Dan Chang, Nanhui Zhang, Yichun Cheng, Shuwang Ge, and Gang Xu. "T Follicular Helper Cells in Tertiary Lymphoid Structure Contribute to Renal Fibrosis by IL-21." International Journal of Molecular Sciences 24, no. 16 (2023): 12535. http://dx.doi.org/10.3390/ijms241612535.

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Tertiary lymphoid structure (TLS) represents lymphocyte clusters in non-lymphoid organs. The formation and maintenance of TLS are dependent on follicular helper T (TFH) cells. However, the role of TFH cells during renal TLS formation and the renal fibrotic process has not been comprehensively elucidated in chronic kidney disease. Here, we detected the circulating TFH cells from 57 IgAN patients and found that the frequency of TFH cells was increased in IgA nephropathy patients with renal TLS and also increased in renal tissues from the ischemic-reperfusion-injury (IRI)-induced TLS model. The i

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Cho, Kyung Serk, Yunhe Liu, Guangsheng Pei, et al. "Abstract 3962: Pan-cancer spatial characterization of tertiary lymphoid structures." Cancer Research 85, no. 8_Supplement_1 (2025): 3962. https://doi.org/10.1158/1538-7445.am2025-3962.

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Abstract Tertiary lymphoid structures (TLS) are frequently observed in various solid tumors, where they play a pivotal role in regulating anti-tumor immune responses. Despite their importance, our understanding of TLS and their interactions with cancer cells within complex tissue environments remains limited. Recent advances in spatial transcriptomics (ST) technology offer new possibilities for investigating the spatial and phenotypic heterogeneity of TLS. We developed TLSphenotyper, a computational framework for automatic TLS segmentation, labeling, extraction, and comprehensive profiling of

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Vaghjiani, Raj G., and Joseph J. Skitzki. "Tertiary Lymphoid Structures as Mediators of Immunotherapy Response." Cancers 14, no. 15 (2022): 3748. http://dx.doi.org/10.3390/cancers14153748.

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Since its first application in the treatment of cancer during the 1800s, immunotherapy has more recently become the leading edge of novel treatment strategies. Even though the efficacy of these agents can at times be predicted by more traditional metrics and biomarkers, often patient responses are variable. TLS are distinct immunologic structures that have been identified on pathologic review of various malignancies and are emerging as important determinants of patient outcome. Their presence, location, composition, and maturity are critically important in a host’s response to malignancy. Beca

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He, Miao, Qihua He, Xiuyu Cai, et al. "Intratumoral tertiary lymphoid structure (TLS) maturation is influenced by draining lymph nodes of lung cancer." Journal for ImmunoTherapy of Cancer 11, no. 4 (2023): e005539. http://dx.doi.org/10.1136/jitc-2022-005539.

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BackgroundTertiary lymphoid structure (TLS) is an organized infiltration of immune cells, showing features of germinal center (GC) commonly seen in secondary lymphoid organs. However, its relationship with tumor-draining lymph nodes (TDLNs) has not been studied and we hypothesized that TDLN may influence maturation of intratumoral TLS in non-small cell lung cancer (NSCLC).MethodsTissue slides of 616 patients that had undergone surgeries were examined. Cox proportional hazard regression model was used to assess risk factors of patients’ survival, and logistic regression model was used for their

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Mizuta, Ryo, Daisuke Muraoka, Ayako Okamura, et al. "10036-IM-3 SPATIAL AND GENOMIC ANALYSES FOR THE CONSTRUCTION OF TERTIARY LYMPHOID STRUCTURE IN GLIOBLASTOMA." Neuro-Oncology Advances 5, Supplement_5 (2023): v5—v6. http://dx.doi.org/10.1093/noajnl/vdad141.020.

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Abstract BACKGROUND Recently, the presence of tertiary lymphoid structure (TLS), composed mainly of intratumoral B cells, has been reported as a favorable prognostic factor in various types of cancer. However, in glioblastoma, TLS has not been well studied though increased B-cell infiltration was likely to be related to improved prognosis. In this study, we performed spatial and genomic analyses in human glioblastoma, focusing on TLS. METHODS We evaluated lymphocytic infiltration by immunostaining in 54 cases. Flow cytometry was conducted on 12 prospective samples. RNA-sequencing (RNA-seq) was

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Trajkovski, Gjorgji, Ljubomir Ognjenovic, Zoran Karadzov, et al. "Tertiary Lymphoid Structures in Colorectal Cancers and Their Prognostic Value." Open Access Macedonian Journal of Medical Sciences 6, no. 10 (2018): 1824–28. http://dx.doi.org/10.3889/oamjms.2018.341.

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Abstract  Introduction: Tumor-infiltrating lymphocytes (TIL) in tumor stroma are considered to be involved in elimination of malignant cells and in prevention of metastasis formation. TIL are consisted of T lymphocytes including cytotoxic lymphocytes that are a constituent part of the effector mechanism of anti-tumor immunity and B lymphocytes that can form tertiary lymphoid structures (TLS). TLS have been described in several solid tumors and in colorectal carcinoma (CRC) and they influence on the local and systemic anti-cancer response. The aim of this study was to quantify the p

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Adoke, Kasimu, and Sanusi Haruna. "10 Tertiary lymphoid structure in pancreatic ductal adenocarcinoma; a potential target in an immunologically inert malignancy." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A10. http://dx.doi.org/10.1136/jitc-2021-sitc2021.010.

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BackgroundTertiary lymphoid structure (TLS) are immune aggregates with various degrees of organization that forms outside of secondary lymphoid organ in response to chronic inflammation, infection or tumours.1 2 TLS like secondary lymphoid organ, has defined T cell zones, B cell zones, high endothelial venules (HEV) and matured dendritic cells. They have been shown to correlate with increase patient survival in many tumours. Pancreatic ductal carcinoma (PDAC) is generally believed to be immunologically inert, low tumour mutation burden (TMB) and poor response to checkpoint blockade. Recent fin

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Krull, Jordan, Anjali Byappanahalli, Yi Jiang, Andrew Gunderson, and Qin Ma. "Abstract 4879: Delineating lymphocyte aggregates from tertiary lymphoid structures using spatial transcriptomics." Cancer Research 84, no. 6_Supplement (2024): 4879. http://dx.doi.org/10.1158/1538-7445.am2024-4879.

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Abstract Tertiary Lymphoid Structures (TLSs) are ectopic lymphoid structures that form in chronically inflamed non-lymphoid tissue. The presence of TLSs in tumors is largely associated with favorable outcomes among patients and also exhibit positive associations with response to immune checkpoint blockade. Although mainly comprised of lymphocytes (B cells and T cells), they are considered a separate entity from lymphocyte aggregates within tissue. Lymphocyte aggregates are fairly routine to identify in H&E stained tissue sections, but delineating TLSs from simple lymphocyte aggregates is s

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Yang, Haihua, Kuifei Chen, Yinan Meng, et al. "Review: radiotherapy-mediated B cells within the TLS influence the tumor microenvironment." Journal for ImmunoTherapy of Cancer 13, no. 7 (2025): e011617. https://doi.org/10.1136/jitc-2025-011617.

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The tumor microenvironment (TME) is a diverse and intricate structure consisting of tumor cells, stromal cells, endothelial cells, and immune cells. It is characterized by the communication between tumor cells and both innate and adaptive immune cells. Tertiary lymphoid structures (TLS) are temporary abnormal collections of lymphoid tissues in which specialized immune responses against tumors can occur. B cells are crucial for the prognostic prediction of various cancers, particularly in response to immunotherapy. There are many types of B cells within the TME, including naive, terminally diff

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Filderman, Jessica, and Walter Storkus. "Therapeutic vascular normalization to promote tumor-associated tertiary lymphoid structures." Journal of Immunology 204, no. 1_Supplement (2020): 89.6. http://dx.doi.org/10.4049/jimmunol.204.supp.89.6.

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Abstract Tertiary lymphoid structures (TLS) are non-encapsulated immune cell aggregates that form at sites of chronic inflammation. Recent studies have shown that the presence of TLS in human tumors indicates positive clinical outcome. However, many tumors have poorly organized and leaky vasculature that impedes entry of immune effector cells into tumors and consequently TLS formation. Recently, studies have shown that low doses of antiangiogenic agents normalize tumor vasculature, leading us to hypothesize that treating tumors with low doses of vascular normalizing (VN) therapies will improve

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Tao, Ping, Zhenyu Wang, Jiongyuan Wang, et al. "Integrated multi-omics analysis reveals immune landscape of tertiary lymphoid structure in retroperitoneal liposarcoma." Journal of Clinical Oncology 42, no. 16_suppl (2024): 11563. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.11563.

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11563 Background: Retroperitoneal liposarcoma (RPLS) is a rare type of mesenchymal tumor characterized by difficult surgical management, immune desert, poor response to immunotherapy and high local recurrence rate. However, how tertiary lymphoid structures (TLS) dictates complex biological processes such as antitumor immunity remains unknown. Thus, we aimed to investigate the spatio-temporal heterogeneity of TLS formation, maturation, and functional involvement in TIME, and the clinical value of TLS in multiple retrospective RPLS clinical cohorts. Methods: 330 patients were retrospectively enr

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Weinstein, Aliyah M., Lu Chen, and Walter J. Storkus. "Modulation of tumor vasculature promotes tertiary lymphoid organogenesis." Journal of Immunology 196, no. 1_Supplement (2016): 213.11. http://dx.doi.org/10.4049/jimmunol.196.supp.213.11.

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Abstract The tumor vasculature has been shown to have pro-tumorigenic effects, leading to the use of anti-angiogenic drugs as therapy. However, the importance of tumor vasculature in recruiting immune cells to the tumor microenvironment (TME), leading to the formation of tertiary lymphoid structures (TLS) within the TME, has also been shown. TLS are aggregates of immune cells that develop at site of chronic inflammation and function as local sites of immune priming. The presence of TLS in the TME is a positive prognostic marker in many human tumors, suggesting that modulation of the tumor vasc

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Chelvanambi, Manoj, Jennifer L. Taylor, Ronald J. Fecek, and Walter J. Storkus. "Therapeutic Induction of Tertiary Lymphoid Structures in Melanoma using STING Agonists." Journal of Immunology 202, no. 1_Supplement (2019): 194.27. http://dx.doi.org/10.4049/jimmunol.202.supp.194.27.

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Abstract Tertiary lymphoid structures (TLS) are non-encapsulated functional aggregates of T cells, B cells, dendritic cells (DC) and high endothelial venules (HEV) located in peripheral sites of chronic inflammation. TLS may serve as sites of local antigen presentation and immune priming that may protect against tumor progression. Homeostatic chemokines CCL19, CCL21 and CXCL13 produced by DCs and/or stromal cells are known to support secondary lymphoid organogenesis and also play key roles in TLS formation. Other DC-associated pro-inflammatory cytokines including lymphotoxin α, IL-36γ and type

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Filderman, Jessica, Manoj Chelvanambi, and Walter Storkus. "584 Therapeutic vascular normalization to promote tumor-associated tertiary lymphoid structures." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A619. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0584.

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BackgroundTertiary lymphoid structures (TLS) are non-encapsulated immune cell aggregates that form at sites of chronic inflammation, including in and around tumors. Recent studies have shown that the presence of TLS in human tumors is an indicator of positive clinical outcome. However, due to dysregulated angiogenesis, many tumors have a poorly-organized and leaky vasculature that impedes entry of immune effector cells into tumors and consequently, TLS formation. It has been shown in pre-clinical studies that low doses of antiangiogenic agents normalize the tumor vasculature, leading us to hyp

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Berthe, Julie, Sriram Sridhar, Felix Segerer, et al. "39 A multi-modal analysis approach leveraging multiplexed spatial phenotyping and multi-omics analysis to better understand the prognostic value of tertiary lymphoid structures in NSCLC." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (2021): A46. http://dx.doi.org/10.1136/jitc-2021-sitc2021.039.

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BackgroundTertiary Lymphoid Structures (TLS) are highly organized ectopic lymphoid structures found in inflamed or tumor tissues, acting as sites of lymphoid recruitment and immune activation. A high TLS density within the tumor is commonly associated with an increased prognostic effect of TILs and with an improved disease free survival and overall survival for patients.1 However, the existence of conflicting studies suggest that multiple TLS features should be taken into account when assessing their prognostic value, such as their location, cellular composition, maturation stage and spatial o

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Li, Mengxi, Jing Cao, Yueheng Wang, Ziru Zhao, Liqiang Ai, and Kejing Zhang. "Predictive power of tertiary lymphoid structure for prognosis and neoadjuvant chemotherapy response in HER2-positive breast cancer." Medicine 104, no. 23 (2025): e42566. https://doi.org/10.1097/md.0000000000042566.

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This study evaluated the prognostic significance of tertiary lymphoid structures (TLS) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on their associations with survival outcomes, response to neoadjuvant therapy, and potential as a biomarker for personalized treatment strategies. Data from patients with HER2-positive BC in the METABRIC and The Cancer Genome Atlas databases were analyzed. TLS expression scores were calculated using gene set variation analysis, and their associations with survival outcomes were assessed. Immune cell infiltration, immune

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Cai, Daming, Heng Yu, Xingzhou Wang, et al. "Turning Tertiary Lymphoid Structures (TLS) into Hot Spots: Values of TLS in Gastrointestinal Tumors." Cancers 15, no. 2 (2023): 367. http://dx.doi.org/10.3390/cancers15020367.

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Tertiary lymphoid structures (TLSs) are ectopic lymphocyte aggregation structures found in the tumor microenvironment (TME). Emerging evidence shows that TLSs are significantly correlated with the progression of gastrointestinal tumors, patients’ prognosis, and the efficacy of adjuvant therapy. Besides, there are still some immunosuppressive factors in the TLSs that may affect the anti-tumor responses of TLSs, including negative regulators of anti-tumor immune responses, the immune checkpoint molecules, and inappropriate tumor metabolism. Therefore, a more comprehensive understanding of TLSs’

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An, Disi, Guoying Chen, Wei Wang, et al. "Abstract 4134: Boosting anti-tumor immunity by promoting high endothelial venule and tertiary lymphoid structure formation in solid tumors via LTBR agonism." Cancer Research 83, no. 7_Supplement (2023): 4134. http://dx.doi.org/10.1158/1538-7445.am2023-4134.

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Abstract High endothelial venules (HEV) are specialized blood vessels that mediate lymphocyte trafficking to lymph nodes. Tertiary lymphoid structures (TLS) are ectopic lymphoid formations that develop in inflamed, infected or tumoral tissues. TLS contain HEV and B cell follicles surrounded by a T-cell zone and are characterized by abundant chemokine expression. The presence of TLS and HEV in solid tumors is positively correlated with patient survival in many cancer types, and may even be predictive of better response to immune-checkpoint blockade. However, the molecular mechanisms underlying

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Huang, Ta-Chen, Cher-Wei Liang, Yu-I. Li, et al. "Abstract 2211: The prognostic role of tertiary lymphoid structure (TLS) in locally advanced esophageal squamous cell carcinoma (ESCC)." Cancer Research 83, no. 7_Supplement (2023): 2211. http://dx.doi.org/10.1158/1538-7445.am2023-2211.

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Abstract Introduction: The presence of TLS in tumors is associated with improved efficacy of immunotherapy in various types of cancer. The significance of TLS in patients with ESCC has been sporadically reported. The study aimed to investigate the prognostic significance of TLS in patients with locally advanced ESCC receiving neoadjuvant chemoradiotherapy (CRT). Patients and Methods: We included two cohorts of locally advanced ESCC patients from two referral centers of Taiwan. Cohort A consisted of 99 patients treated with paclitaxel/cisplatin-based CRT, 69 of them being neoadjuvant CRT and 30

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Chen, Yulu, Yuhao Wu, Guorong Yan, and Guolong Zhang. "Tertiary lymphoid structures in cancer: maturation and induction." Frontiers in Immunology 15 (April 16, 2024). http://dx.doi.org/10.3389/fimmu.2024.1369626.

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Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumor-associated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value in various cancers. In recent years, the concept of maturity regarding TLS has been proposed and mature TLS, characterized by well-developed germinal centers, exhibits a more potent tumor-suppressive capacity with stronger significance. Meanwhile, more and more evidence show

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Rochefort, Juliette, Gilles Marodon, Jean‐Luc Teillaud, and Marie‐Caroline Dieu‐Nosjean. "The Sunrise of Tertiary Lymphoid Structures in Cancer." Immunological Reviews 332, no. 1 (2025). https://doi.org/10.1111/imr.70046.

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ABSTRACTFirst considered as a negative epiphenomenon in autoimmune and inflammatory diseases, with possible deleterious consequences through the production of pathological autoantibodies and antiself T cells, tertiary lymphoid structures (TLS) have gained major scientific and clinical interest in cancer due to their association with better clinical outcomes and improved responses to immunotherapy. Studies have investigated the structure and plasticity of TLS in the context of tumors and the role of the TLS B‐cell compartment in contributing to the favorable clinical outcome of cancer patients.

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Goronzy, Jörg J., and Cornelia M. Weyand. "Perivascular Tertiary Lymphoid Structures in Autoimmune Disease." Immunological Reviews 332, no. 1 (2025). https://doi.org/10.1111/imr.70047.

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ABSTRACTImmunotherapy of autoimmune diseases has expanded substantially, yet autoimmunity remains incurable, and patients suffer from chronic destructive tissue inflammation that fails to resolve. Mechanisms underlying the endurance of autoimmune memory and the lack of exhaustion are beginning to be understood. Here, we review emerging data on how decentralization of cellular immunity contributes to persistent autoimmune responses and chronicity of autoimmune tissue inflammation. Two processes are recognized as ensuring lasting immune memory: the generation of tissue‐resident memory T cells (T

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Salem, Deepak, Manoj Chelvanambi, Walter J. Storkus, and Ronald J. Fecek. "Cutaneous Melanoma: Mutational Status and Potential Links to Tertiary Lymphoid Structure Formation." Frontiers in Immunology 12 (March 4, 2021). http://dx.doi.org/10.3389/fimmu.2021.629519.

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Recent advances in immunotherapy have enabled rapid evolution of novel interventional approaches designed to reinvigorate and expand patient immune responses against cancer. An emerging approach in cancer immunology involves the conditional induction of tertiary lymphoid structures (TLS), which are non-encapsulated ectopic lymphoid structures forming at sites of chronic, pathologic inflammation. Cutaneous melanoma (CM), a highly-immunogenic form of solid cancer, continues to rise in both incidence and mortality rate, with recent reports supporting a positive correlation between the presence of

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Vaccaro, Alessandra, Tiarne van de Walle, Mohanraj Ramachandran, Magnus Essand, and Anna Dimberg. "Of mice and lymphoid aggregates: modeling tertiary lymphoid structures in cancer." Frontiers in Immunology 14 (October 26, 2023). http://dx.doi.org/10.3389/fimmu.2023.1275378.

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Tertiary lymphoid structures (TLS) are lymph node-like aggregates that can form in association with chronic inflammation or cancer. Mature TLS are organized into B and T cell zones, and are not encapsulated but include all cell types necessary for eliciting an adaptive immune response. TLS have been observed in various cancer types and are generally associated with a positive prognosis as well as increased sensitivity to cancer immunotherapy. However, a comprehensive understanding of the roles of TLS in eliciting anti-tumor immunity as well as the mechanisms involved in their formation and fun

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Li, Qunxing, Xiangqi Liu, Dikan Wang, et al. "Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma." International Journal of Oral Science 12, no. 1 (2020). http://dx.doi.org/10.1038/s41368-020-00092-3.

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Abstract Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-ne

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Khanal, Shrijan, Andreas Wieland, and Andrew J. Gunderson. "Mechanisms of tertiary lymphoid structure formation: cooperation between inflammation and antigenicity." Frontiers in Immunology 14 (September 21, 2023). http://dx.doi.org/10.3389/fimmu.2023.1267654.

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To mount an effective anti-tumor immune response capable of controlling or eliminating disease, sufficient numbers of lymphocytes must be recruited to malignant tissue and allowed to sustain their effector functions. Indeed, higher infiltration of T and B cells in tumor tissue, often referred to as “hot tumors”, is prognostic for patient survival and predictive of response to immunotherapy in almost all cancer types. The organization of tertiary lymphoid structures (TLS) in solid tumors is a unique example of a hot tumor whereby T and B lymphocytes aggregate with antigen presenting cells and h

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Schumacher, Ton N., and Daniela S. Thommen. "Tertiary lymphoid structures in cancer." Science 375, no. 6576 (2022). http://dx.doi.org/10.1126/science.abf9419.

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Tertiary lymphoid structures in cancer Tertiary lymphoid structures (TLSs) are lymphoid formations that are found in nonlymphoid tissues. TLS can develop in inflamed tissues and are associated with chronic inflammatory disorders, autoimmunity, and cancer. In the setting of tumors, TLSs facilitate the influx of immune cells into the tumor site and have therefore attracted interest as a means of improving anticancer immunity and favorable treatment response in patients. Schumacher and Thommen review the biology of TLSs and outline recent advances in TLS research. They discuss how TLSs are detect

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You, Xin, Kristina Koop, and Andreas Weigert. "Heterogeneity of tertiary lymphoid structures in cancer." Frontiers in Immunology 14 (December 4, 2023). http://dx.doi.org/10.3389/fimmu.2023.1286850.

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The success of immunotherapy approaches, such as immune checkpoint blockade and cellular immunotherapy with genetically modified lymphocytes, has firmly embedded the immune system in the roadmap for combating cancer. Unfortunately, the majority of cancer patients do not yet benefit from these therapeutic approaches, even when the prognostic relevance of the immune response in their tumor entity has been demonstrated. Therefore, there is a justified need to explore new strategies for inducing anti-tumor immunity. The recent connection between the formation of ectopic lymphoid aggregates at tumo

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Komura, Kazumasa, Satoshi Tokushige, Mitsuaki Ishida, et al. "Tertiary lymphoid structure and neutrophil–lymphocyte ratio coordinately predict outcome of pembrolizumab." Cancer Science, September 26, 2023. http://dx.doi.org/10.1111/cas.15976.

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AbstractEmerging evidence suggests that the presence of tertiary lymphoid structures (TLS) and neutrophil–lymphocyte ratio (NLR) in peripheral blood is associated with the treatment response to checkpoint inhibitors (CPIs), whereas there is limited knowledge regarding whether these factors reciprocally impact the treatment outcomes of CPIs in metastatic urothelial carcinoma (mUC). Herein, we investigated treatment outcomes of platinum‐refractory mUC patients (50 cases with whole‐exome and transcriptome sequencing) treated with pembrolizumab. The pathological review identified 24% of cases of T

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Wu, Sixuan, Junfan Pan, Qihong Pan, Lijun Zeng, Renji Liang, and Yuehua Li. "Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma." Frontiers in Immunology 15 (September 19, 2024). http://dx.doi.org/10.3389/fimmu.2024.1453220.

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Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood. Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene sub

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Yu, Aoyang, Menghan Cao, Kaile Zhang, et al. "The prognostic value of the tertiary lymphoid structure in gastrointestinal cancers." Frontiers in Immunology 14 (October 6, 2023). http://dx.doi.org/10.3389/fimmu.2023.1256355.

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BackgroundNumerous studies and research papers have provided evidence suggesting that tertiary lymphoid structures (TLS) play a crucial role in combating and suppressing tumor growth and progression. Despite the wealth of information on the significance of TLS in various types of cancer, their prognostic value in gastrointestinal (GI) cancers remains uncertain. Therefore, this meta-analysis investigated the prognostic value of TLS in GI cancers.MethodsWe searched Web of science, Pubmed, Embase and Cochrane Library for studies that met the requirements as of May 1, 2023, and the hazard ratio (H

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Li, Ruiqi, Fan Gu, Linlin Peng, et al. "Tertiary Lymphoid Structure in Dental Pulp: The Role in Combating Bacterial Infections." Advanced Science, October 28, 2024. http://dx.doi.org/10.1002/advs.202406684.

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AbstractTertiary lymphoid structure (TLS) is associated with various pathologies, including those of cancers and chronic infections. Depending on the organ, multiple factors regulate the formation of TLS. However, the role of TLS in immune response and the molecules that drive its formation remain uncertain. The dental pulp, includes a few immune cells surrounded by rigid mineralized tissue, and opens to the outside through the apical foramen. Owing to this special organization, the dental pulp generates a directional immune response to bacterial infection. Considering this aspect, the dental

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Zhai, Ke, Yuting Ma, Xue Gao, Kun Ru, and Miaoqing Zhao. "Tertiary lymphoid structures in esophageal cancer: a novel target for immunotherapy." Frontiers in Immunology 16 (June 4, 2025). https://doi.org/10.3389/fimmu.2025.1543322.

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Esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), which is the most common subtype in China, is one of the most aggressive gastrointestinal malignancies. Traditional treatments like surgery, radiotherapy, and chemotherapy have limited success, but the study of tertiary lymphoid structure (TLS) has opened new avenues for immunotherapy. TLS is an ectopic immune cell cluster, including B cells, T cells, and dendritic cells (DCs), that forms in chronic inflammation such as tumors. TLS is often found at tumor invasion margins and is linked to better prognosis in EC patie

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Zhao, Ruibo, Jinghe Zhang, Jialu Ma, et al. "cGAS-activated endothelial cell–T cell cross-talk initiates tertiary lymphoid structure formation." Science Immunology 9, no. 98 (2024). http://dx.doi.org/10.1126/sciimmunol.adk2612.

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Aberrant activation of the cyclic guanosine monophosphate–adenosine monophosphate synthase–stimulator of interferon genes (cGAS-STING) pathway causes autoimmunity in humans and mice; however, the exact mechanism by which the cGAS-STING pathway initiates adaptive immunity and tissue pathology is still not fully understood. Here, we used a cGAS knockin (KI) mouse model that develops systemic autoimmunity. In the lungs of cGAS-KI mice, blood vessels were enclosed by organized lymphoid tissues that resemble tertiary lymphoid structures (TLSs). Cell-intrinsic cGAS induction promoted up-regulation o

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Li, Shuling, Kuifei Chen, Zhenwei Sun, et al. "Radiation drives tertiary lymphoid structures to reshape TME for synergized antitumour immunity." Expert Reviews in Molecular Medicine 26 (2024). http://dx.doi.org/10.1017/erm.2024.27.

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Abstract Radiotherapy (RT) plays a key role in the tumour microenvironment (TME), impacting the immune response via cellular and humoral immunity. RT can induce local immunity to modify the TME. It can stimulate dendritic cell maturation and T-cell infiltration. Moreover, B cells, macrophages and other immune cells may also be affected. Tertiary lymphoid structure (TLS) is a unique structure within the TME and a class of aggregates containing T cells, B cells and other immune cells. The maturation of TLS is determined by the presence of mature dendritic cells, the density of TLS is determined

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Tang, Han, Zhengwei Su, Qingming Huang, et al. "A model of tertiary lymphatic structure-related prognosis for penile squamous cell carcinoma." BMC Urology 24, no. 1 (2024). http://dx.doi.org/10.1186/s12894-024-01532-6.

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Abstract Background We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC). Methods We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan–Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis. Result BMI, T, N,

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Xi, Ningyuan, Xiaoxiang Xu, Mingyuan Xu, et al. "The clinical and pathological significance of tertiary lymphoid structure in extramammary Paget's disease." Frontiers in Immunology 15 (November 15, 2024). http://dx.doi.org/10.3389/fimmu.2024.1435629.

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BackgroundTumor-associated tertiary lymphoid structures (TLSs) are functional immune-responsive aggregates, which have been reported to be associated with better prognosis in various tumors. However, their exact characteristics and prognostic value in extramammary Paget’s disease (EMPD) remain unknown.ObjectiveTo explore the features of TLSs in EMPD and their association with clinicopathological characteristics.MethodsIn total, 171 EMPD patients from 2015 to 2023, retrospective, single center cohort were collected to assess the presence, maturation status, and location of TLSs by immunohistoch

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