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Journal articles on the topic 'Tertiary lymphoid structure'

Author: Grafiati

Published: 30 November 2024

Last updated: 31 July 2025

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1

Cook, Seungho, Haenara Shin, Mi-Kyoung Seo, Dae Seung Lee, and Hongyoon Choi. "Abstract 5420: Deep learning-based mapping of tertiary lymphoid structure scores from H&E images of renal cell carcinoma trained by spatial transcriptomics data." Cancer Research 83, no. 7_Supplement (2023): 5420. http://dx.doi.org/10.1158/1538-7445.am2023-5420.

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Abstract Purpose Tertiary lymphoid structures are organized aggregates of immune cells present in the tumor microenvironment (TME) in which novel targets as well as beneficial biomarkers for immunotherapy in cancer were found. Here, we have developed and validated a deep learning model by integrating H&E images of renal cell carcinoma and spatial transcriptomics data to infer spatial mapping of tertiary lymphoid structure scores in TME only using hematoxylin and eosin (H&E) images. Methods A total of 20 H&E images combined with spatial transcriptomics data of renal cell carcinoma w

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2

Rustamkhanov, R. A., K. Sh Gantsev, and D. S. Tursumetov. "Tertiary Lymphoid Structures and Cancer Prognosis (Brief Review)." Creative surgery and oncology 9, no. 4 (2020): 293–96. http://dx.doi.org/10.24060/2076-3093-2019-9-4-293-296.

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This brief review is devoted to the role of tertiary lymphoid structures in oncological processes. A number of research studies carried out over the past ten years have shed light on the functions of such structures in various diseases, as well as their role in the progression of the pathological process or resolution of a disease. The data presented in some research works confirms the relationship between the presence of tumour-specific (tumour-associated) tertiary lymphoid structures and a favourable prognosis in patients with various oncological diseases, which suggests the participation of

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3

Robles, Marcel R., Michael Malkowski, and Sandeep Krishnan. "S1842 Tertiary Lymphoid Structure Mimicking Pancreatic Mass." American Journal of Gastroenterology 117, no. 10S (2022): e1285-e1286. http://dx.doi.org/10.14309/01.ajg.0000864008.96774.a4.

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4

Evans, Isabel, and Mi-Yeon Kim. "Involvement of lymphoid inducer cells in the development of secondary and tertiary lymphoid structure." BMB Reports 42, no. 4 (2009): 189–93. http://dx.doi.org/10.5483/bmbrep.2009.42.4.189.

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5

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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6

Zhou, Xingwang, Wenyan Li, Jie Yang, et al. "Tertiary lymphoid structure stratifies glioma into three distinct tumor subtypes." Aging 13, no. 24 (2021): 26063–94. http://dx.doi.org/10.18632/aging.203798.

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7

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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Sunyer, J. Oriol, Yasuhiro Shibasali, Fumio Takizawa, Ding Yang, Pierre Boudinot, and Aleksei Krasnov. "IDENTIFICATION OF PRIMORDIAL ORGANIZED LYMPHOID STRUCTURE IN THE SPLEEN OF TELEOST FISH." Journal of Immunology 204, no. 1_Supplement (2020): 92.40. http://dx.doi.org/10.4049/jimmunol.204.supp.92.40.

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Abstract Induction of adaptive immune responses in higher vertebrate species occur within organized lymphoid structures (e.g. lymph nodes, Peyer’s patches). It has been proposed that such structures emerged throughout evolutionary time with the goal to maximize encounters between antigens, antigens-presenting cells and B-T lymphocytes. Fish lack such structures and thus, it remains unknown how and where antigen-specific immunoglobulin responses are induced in these species. To understand how systemic immune responses are induced in teleost lymphoid organs, Rainbow Trout were immunized with sev

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9

Denton, Alice E., Silvia Innocentin, Edward J. Carr, et al. "Type I interferon induces CXCL13 to support ectopic germinal center formation." Journal of Experimental Medicine 216, no. 3 (2019): 621–37. http://dx.doi.org/10.1084/jem.20181216.

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Ectopic lymphoid structures form in a wide range of inflammatory conditions, including infection, autoimmune disease, and cancer. In the context of infection, this response can be beneficial for the host: influenza A virus infection–induced pulmonary ectopic germinal centers give rise to more broadly cross-reactive antibody responses, thereby generating cross-strain protection. However, despite the ubiquity of ectopic lymphoid structures and their role in both health and disease, little is known about the mechanisms by which inflammation is able to convert a peripheral tissue into one that res

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10

van der Leun, Anne M. "Tertiary lymphoid structure formation: A matter of tumor-immune co-evolution." Molecular Immunology 175 (November 2024): 143–45. http://dx.doi.org/10.1016/j.molimm.2024.09.012.

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11

HAYASE, SHIMON, NORIKATSU MIYOSHI, SHIKI FUJINO, et al. "Fibroblast Activation Protein and Tertiary Lymphoid Structure in Colorectal Cancer Recurrence." Anticancer Research 42, no. 12 (2022): 5897–907. http://dx.doi.org/10.21873/anticanres.16099.

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12

Briem, Oscar, Eva Källberg, Siker Kimbung, et al. "CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer." Cancers 15, no. 4 (2023): 1262. http://dx.doi.org/10.3390/cancers15041262.

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The presence of CD169+ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169+ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169+ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169+/TLLS in PTs correlated with

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13

Erlich, Emma, Rafael Czepielewski, Shashi Kumar, et al. "B cells drive tertiary lymphoid organ formation in ileal inflammation." Journal of Immunology 208, no. 1_Supplement (2022): 113.18. http://dx.doi.org/10.4049/jimmunol.208.supp.113.18.

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Abstract Crohn’s disease [CD] is one of the two most common forms of inflammatory bowel disease, affecting over half a million Americans. Like many other diseases with chronic inflammation, some patients with CD develop tertiary lymphoid organs [TLO] in areas of the gastrointestinal tract with active disease. TLOs are organized clusters of lymphocytes, similar in structure to secondary lymphoid organs, though they develop after birth and their contribution to pathogenesis in CD, or other diseases, is unclear. We, and others, have also found B cell rich lymphoid aggregates in the mesenteric fat

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14

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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15

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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Jiang, Quan, Chenyu Tian, Hao Wu, et al. "Tertiary lymphoid structure patterns predicted anti-PD1 therapeutic responses in gastric cancer." Chinese Journal of Cancer Research 34, no. 3 (2022): 365–82. http://dx.doi.org/10.21147/j.issn.1000-9604.2022.04.05.

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17

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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18

Hill, David G., Liang Yu, Hugh Gao, et al. "Hyperactive gp130/STAT3-driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development." International Journal of Cancer 143, no. 1 (2018): 167–78. http://dx.doi.org/10.1002/ijc.31298.

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19

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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20

Ichii, Osamu, Marina Hosotani, Md Abdul Masum, et al. "Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis." Journal of the American Society of Nephrology 33, no. 1 (2021): 88–107. http://dx.doi.org/10.1681/asn.2021040575.

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BackgroundKidneys with chronic inflammation develop tertiary lymphoid structures (TLSs). Infectious pyelonephritis is characterized by renal pelvis (RP) inflammation. However, the pathologic features of TLSs, including their formation and association with non-infectious nephritis, are unclear.MethodsRPs from humans and mice that were healthy or had non-infectious chronic nephritis were analyzed for TLS development, and the mechanism of TLS formation investigated using urothelium or lymphoid structure cultures.ResultsRegardless of infection, TLSs in the RP, termed urinary tract–associated lymph

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21

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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22

Daya, Khodor Abou, Daqiang Zhao, Kyle Biery, and Martin H. Oberbarnscheidt. "Tertiary lymphoid organs in renal chronic allograft rejection." Journal of Immunology 204, no. 1_Supplement (2020): 161.14. http://dx.doi.org/10.4049/jimmunol.204.supp.161.14.

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Abstract Chronic allograft rejection remains a major obstacle to long-term allograft survival. The immunologic role of tertiary lymphoid organs (TLO) in allograft rejection is unclear. Here, we employed a chronic renal allograft rejection model in mice and intravital 2-photon microscopy to investigate the function of TLO in transplant rejection. CB6F1 (F1) RIP-LTα (preformed TLO) or F1 (no TLO) kidney grafts were transplanted to WT B6 recipients and survival monitored. To investigate immunologic function of TLO, we adoptively transferred B6-RIPLTα CD11c-YFP mice with 10m naïve dsRed OT-I T cel

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23

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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24

Yamamoto, Shinya, and Motoko Yanagita. "A Novel Pathological Mechanism of Tertiary Lymphoid Structure Formation in the Renal Pelvis." Journal of the American Society of Nephrology 33, no. 1 (2021): 4–6. http://dx.doi.org/10.1681/asn.2021111465.

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25

Wang, Jin, Dongbo Jiang, Xiaoqi Zheng, et al. "Tertiary lymphoid structure and decreased CD8+ T cell infiltration in minimally invasive adenocarcinoma." iScience 25, no. 3 (2022): 103883. http://dx.doi.org/10.1016/j.isci.2022.103883.

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26

雷, 鑫焌. "Research Progress of Tertiary Lymphoid Structure and Tumor-Associated Macrophages in Hepatocellular Carcinoma." Advances in Clinical Medicine 12, no. 02 (2022): 1067–73. http://dx.doi.org/10.12677/acm.2022.122157.

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27

Schroeder, A., F. Zhu, and H. Hu. "LB867 Development of tertiary lymphoid structure in dermal tumors and anti-tumor immunity." Journal of Investigative Dermatology 144, no. 8 (2024): S151. http://dx.doi.org/10.1016/j.jid.2024.06.1247.

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28

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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Ota, Yosuke, Kimiya Matsuda, Hiroki Umehara, and Hitoshi Ban. "Abstract LB125: Increased expression of tertiary lymphoid structure related genes contributes the strong anti-tumor activity of 5DEX-0509R that is dextran conjugated TLR7 agonist targeting TAM." Cancer Research 85, no. 8_Supplement_2 (2025): LB125. https://doi.org/10.1158/1538-7445.am2025-lb125.

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Abstract Introduction: Toll-like Receptors (TLRs) are a class of Pattern Recognition Receptors (PRRs) capable of recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Since TLR activation in the tumor initiates anti-tumor immune responses, TLR agonists are an attractive target and are still actively studied in cancer immunotherapy. We have reported that 5DEX-0509R, a TLR7 agonist targeting Tumor-Associated Macrophages (TAMs), demonstrates selective delivery to TAMs and strongly shifts their phenotype from M2-like to M1-like, resulting in a

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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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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, Jiahui Jiang, Daiwei Zhang, et al. "Abstract 7424: iStarTLS: Advanced detection and phenotyping of tertiary lymphoid structures." Cancer Research 84, no. 6_Supplement (2024): 7424. http://dx.doi.org/10.1158/1538-7445.am2024-7424.

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Abstract Tertiary lymphoid structures (TLSs) are clusters of immune cells formed in non-lymphoid tissues. They are often found at sites of chronic inflammation, notably within the invasive margins and the core of various solid tumors. TLSs are pivotal in mediating anti-tumor immunity. However, our understanding of TLSs in large/complex tissue contexts remains incomplete due to the lack of computational tools to effectively detect and phenotype TLSs. Recent advances in spatially resolved transcriptomics (SRT) present a broader spectrum of analytical possibilities for investigating the spatial p

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Zhao, Zhan, Hui Ding, Zheng-bin Lin, et al. "Relationship between Tertiary Lymphoid Structure and the Prognosis and Clinicopathologic Characteristics in Solid Tumors." International Journal of Medical Sciences 18, no. 11 (2021): 2327–38. http://dx.doi.org/10.7150/ijms.56347.

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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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Buisseret, Laurence, Christine Desmedt, Soizic Garaud, et al. "Reliability of tumor-infiltrating lymphocyte and tertiary lymphoid structure assessment in human breast cancer." Modern Pathology 30, no. 9 (2017): 1204–12. http://dx.doi.org/10.1038/modpathol.2017.43.

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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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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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Chung, Shin-Yi, Ming-Huang Chen, Yi-Chen Yeh, Yu-Chan Chang, and Yu-Cha Wang. "Abstract 1527: Exploring the role of tertiary lymphoid structure in the tumor microenvironment of cholangiocarcinoma." Cancer Research 84, no. 6_Supplement (2024): 1527. http://dx.doi.org/10.1158/1538-7445.am2024-1527.

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Abstract Cholangiocarcinoma is the second most common hepatobiliary malignant tumor besides liver cancer, grows from bile duct epithelial cells. However, surgery is the only hope for most patients with cholangiocarcinoma, but the effectiveness of treatment is not outstanding. Even though other methods of treatment, such as chemotherapy and radiation therapy, have limited effects. The immunotherapy and precision treatment have become the latest expectations of patients. Here, we analyzed the TCGA and GEO database to classify the cold and hot tumor using hierarchical clustering. The MCP counter

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Gomez Medellin, Jorge E., Maile Kananiokala Hollinger, Jillian Rosenberg, et al. "VEGFR3-driven pulmonary lymphangiogenesis exacerbates induction of bronchus-associated lymphoid tissue in allergic airway disease." Journal of Immunology 208, no. 1_Supplement (2022): 109.24. http://dx.doi.org/10.4049/jimmunol.208.supp.109.24.

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Abstract Asthmatic lung samples present with both a higher density of pulmonary lymphatic vessels and a higher incidence of bronchus associated lymphoid tissue (BALT). Here, we asked whether lymphangiogenesis, stimulated by the VEGF-C/VEGFR-3 signaling axis in lymphatic endothelial cells (LECs), plays a role in promoting BALT in mouse models of allergy. First, we determined that chronic intratracheal instillation of house dust mite (HDM), a clinically relevant allergen, recapitulates both lymphangiogenesis and BALT induction. Intratracheal stimulation of VEGFR-3 in LECs exacerbated BALT, while

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Hou, Yue, Sijing Qiao, Miao Li, et al. "The gene signature of tertiary lymphoid structures within ovarian cancer predicts the prognosis and immunotherapy benefit." Frontiers in Genetics 13 (January 10, 2023). http://dx.doi.org/10.3389/fgene.2022.1090640.

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Ovarian cancer (OC) has the lowest survival rate among gynecologic malignancies. Ectopic lymphocyte aggregates, namely tertiary lymphoid structures (TLSs), have been reported as positive biomarkers for tumor prognosis. However, the related gene signature of tertiary lymphoid structure in ovarian cancer was less understood. Therefore, this study first exhibited the organizational patterns of tertiary lymphoid structure by H&amp;E staining and immunohistochemistry (IHC), and confirmed the improved survival values of tertiary lymphoid structure and quantified tumor-infiltrating lymphocytes (C

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Palmer, Mitchell V., Douglas E. Jones, Nicholas J. Bockenstedt, and Paola M. Boggiatto. "Tertiary lymphoid structures in pulmonary granulomas of cattle experimentally infected with aerosolized Mycobacterium bovis." BMC Veterinary Research 21, no. 1 (2025). https://doi.org/10.1186/s12917-025-04804-x.

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Abstract Mycobacterium bovis is the primary cause of tuberculosis in animals, most notably cattle. In cattle and other susceptible hosts, the hallmark lesion of tuberculosis is the granuloma. Granulomas represent the host–pathogen interface where disease outcome is determined; therefore, it is critical to understand host–pathogen interactions at the granuloma level. Granulomas are highly structured lesions with distinct cellular compartments for T cells, macrophages, multinucleated giant cells, and B cells. A recognized but poorly understood morphologic feature of many granulomas is the presen

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Nayar, Saba, Jason D. Turner, Saba Asam, et al. "Molecular and spatial analysis of tertiary lymphoid structures in Sjogren’s syndrome." Nature Communications 16, no. 1 (2025). https://doi.org/10.1038/s41467-024-54686-0.

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AbstractTertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren’s disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lym

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"Tryptophan Metabolism Regulates Tertiary Lymphoid Structure Maturation." Cancer Discovery, 2025. https://doi.org/10.1158/2159-8290.cd-rw2025-061.

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Liu, Yang, Shuang-Yan Ye, Shuai He, et al. "Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma." Nature Communications 15, no. 1 (2024). http://dx.doi.org/10.1038/s41467-024-52153-4.

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AbstractTertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T

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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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Hein, Ashley L., Natasha Singh, and Samuel M. Cohen. "Small Intestinal Adenocarcinoma Involving a Submucosal Ectopic Lymph Node: A Case Report." International Journal of Surgical Pathology, October 19, 2023. http://dx.doi.org/10.1177/10668969231204970.

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An 83-year-old male with a 55-year history of Crohn's disease, ileocecectomy 40 years prior, and naturopathic treatment for 25 years, presented with nausea, vomiting, and abdominal pain. Computed tomography of abdomen and pelvis demonstrated partial small intestinal obstruction and a 4.4-cm solid left renal mass. After 3 months of recurrent intestinal obstruction and development of a pericolonic abscess, resection of the ileocolonic anastomosis, abscess, and partial nephrectomy were performed. Histopathology demonstrated chronic active enteritis with fistula tract formation, consistent with Cr

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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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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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"Disease Site Dictates Tertiary Lymphoid Structure Activity in Ovarian Cancer." Cancer Discovery, 2024. http://dx.doi.org/10.1158/2159-8290.cd-rw2024-130.

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