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Journal articles on the topic 'Structure lymphoide tertiaire (TLS)'

Author: Grafiati
Published: 23 November 2024
Last updated: 31 July 2025

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1

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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2

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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3

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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4

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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5

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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6

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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7

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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8

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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9

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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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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11

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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12

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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13

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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14

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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15

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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16

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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17

Kushnarev, Vladimir, Daniil Dymov, Nadezhda Lukashevich, et al. "Abstract P6-04-15: AI-based prediction of tertiary lymphoid structures and lymphocyte immune infiltration in breast carcinomas." Cancer Research 83, no. 5_Supplement (2023): P6–04–15—P6–04–15. http://dx.doi.org/10.1158/1538-7445.sabcs22-p6-04-15.

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Abstract Introduction Tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs) in breast carcinomas are prognostic for survival and predictive of certain therapy responses. The presence of TLSs and TILs are identified by manual pathological examination; however, this method often lacks reproducibility, limiting its use in routine clinical practice. Here, we demonstrate that morphological evaluation of whole slide images (WSIs) using an artificial intelligence (AI)-based analytic workflow comprised of convolutional neural network (CNN) deep learning models that accurately a
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18

Li, Jianhui, Ye Nie, Weili Jia, Wenlong Wu, Wenjie Song, and Yongxiang Li. "Effect of Tertiary Lymphoid Structures on Prognosis of Patients with Hepatocellular Carcinoma and Preliminary Exploration of Its Formation Mechanism." Cancers 14, no. 20 (2022): 5157. http://dx.doi.org/10.3390/cancers14205157.

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Background: Tertiary lymphoid structures (TLSs) are formed by the aggregation of tumour-infiltrating lymphocytes (TILs), which is driven by chemokines or cytokines in the tumour microenvironment. Studies have shown that TLSs are associated with good prognosis in patients with various solid tumours and can improve patient responses to immunotherapy. However, the role of TLSs in hepatocellular carcinoma (HCC) remains controversial, and the underlying molecular mechanism is unclear. Methods: According to haematoxylin-eosin (HE) staining results, HCC patients in Xijing Hospital data and TCGA data
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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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20

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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21

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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Zeng, Zheng, Yee Man Au-Yeung, and Jiandong Huang. "Abstract 7466: Exploring tertiary lymphoid structures and immune cell interactions in gastric cancer prognosis." Cancer Research 84, no. 6_Supplement (2024): 7466. http://dx.doi.org/10.1158/1538-7445.am2024-7466.

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Abstract Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates found in chronically inflamed, infected, and tumor tissues. Prior research indicates that the presence of TLS and tumor-infiltrating lymphocytes (TILs) correlates with a more favorable prognosis in several cancers. Our study investigates the role of TLSs and TILs in gastric cancer, the 4th leading cause of cancer-related death worldwide. We analyzed tumor samples from 107 late-stage gastric cancer patients from mainland China, with a 5-year follow-up period. We performed H&E and multiplex immunofluorescence staini
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Narvaez, Dana, Jorge Nadal, Adrian Nervo, et al. "The Emerging Role of Tertiary Lymphoid Structures in Breast Cancer: A Narrative Review." Cancers 16, no. 2 (2024): 396. http://dx.doi.org/10.3390/cancers16020396.

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This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, and prognostic value, and current ways of recognizing them. A comprehensive literature review was performed using the PubMed/Medline, Scopus, and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response. In this context
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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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25

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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Hummelink, Karlijn, Vincent van der Noort, Mirte Muller, et al. "Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer." PLOS ONE 19, no. 7 (2024): e0293707. http://dx.doi.org/10.1371/journal.pone.0293707.

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Background The efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab. Methods Pretreatment samples from 135 patients receiving nivolumab were used to evaluate the predictive performance of CD8 tumor-infiltrating lymphocytes (TILs), intratumoral (IT) localization of CD8 TILs
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Nader, Noor, Elaine Byrnes, Sheryl Kunning, et al. "Abstract B005: Lymphoid aggregates dictate immune activity in melanoma and lung brain metastases." Cancer Research 84, no. 5_Supplement_1 (2024): B005. http://dx.doi.org/10.1158/1538-7445.brain23-b005.

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Abstract Brain metastasis is the cause of death of more than 40% of all cancer patients and is five times more prevalent than primary brain tumors. Melanoma, lung, and breast cancers are the three most common cancers metastasizing to the brain. Currently, radiation and chemotherapy are the gold standard for the treatment of brain metastasis. However, despite the efficacy of current T cell-based immunotherapies in primary cancers, recent clinical trials have demonstrated little to no benefit in brain metastasis patients. Thus, we predict that tertiary lymphoid structures (TLS) could provide the
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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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Zebboudj, Abderezak, Masataka Amisaki, Hiroshi Yano, et al. "Abstract B079: Interleukin-33 activated ILC2s induce tertiary lymphoid structures in pancreatic cancer." Cancer Immunology Research 13, no. 2_Supplement (2025): B079. https://doi.org/10.1158/2326-6074.io2025-b079.

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Abstract Background: Tertiary lymphoid structures (TLS) are ectopic immune cell aggregates in tumors that correlate with enhanced immunity and prognosis. Although TLS form via lymphotoxin (LT)-LTβR signaling, the TLS inducing molecules and cells remain unclear. Approach: To identify TLS inducing signals, we use pancreatic ductal adenocarcinoma (PDAC), a cold tumor where increased TLS density correlates with enhanced survival. To discover novel TLS inducers, we analyze bulk transcriptomes from human PDAC and 12 cold and hot cancers. We dissect the mechanisms in a Kras/p53-driven orthotopic PDAC
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Cheng, Na, Peng Li, Huanhuan Cheng, et al. "Prognostic Value of Tumor-Infiltrating Lymphocytes and Tertiary Lymphoid Structures in Epstein-Barr Virus-Associated and -Negative Gastric Carcinoma." Frontiers in Immunology 12 (July 1, 2021). http://dx.doi.org/10.3389/fimmu.2021.692859.

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BackgroundTumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response against cancer and tertiary lymphoid structures (TLS) may contribute to lymphocytes recruitment. Both of them have been reported as potential prognostic parameters in some human malignancies. However, the roles of TILs, TLS, and their correlation in Epstein-Barr Virus-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC) are largely unknown.MethodsTo observe the correlation among TILs, TLS, and clinicopathological characteristics and their prognostic significan
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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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32

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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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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34

"Probing Microbiome, TLS Dynamics in Tumors." Cancer Discovery, December 5, 2022, OF1. http://dx.doi.org/10.1158/2159-8290.cd-nb2022-0077.

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Abstract Across several cancer types, researchers have identified distinct gut microbial features that are associated with a high density of intratumoral tertiary lymphoid structures. They hope to develop microbiome-based interventions that induce the formation of more of these structures, which correlate with immune checkpoint blockade responsiveness.
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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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Boissière-Michot, Florence, Marie-Christine Chateau, Simon Thézenas, et al. "Prognostic value of tertiary lymphoid structures in triple-negative breast cancer: integrated analysis with the tumor microenvironment and clinicopathological features." Frontiers in Immunology 15 (December 12, 2024). https://doi.org/10.3389/fimmu.2024.1507371.

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BackgroundIn triple-negative breast cancer (TNBC), the most immunogenic breast cancer type, tumor-infiltrating lymphocytes (TILs) are an independent prognostic factor. Tertiary lymphoid structures (TLS) are an important TILs source, but they are not integrated in the current prognostic criteria.MethodsIn this retrospective study, TLS were assessed in hematein-eosin-saffron-stained (HES) histological sections from 397 early, chemotherapy-naive TNBC samples after primary surgical resection. Their association with i) classical clinicopathological features, ii) TILs and CD3+, CD8+, CD20+ lymphoid
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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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39

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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Zhao, Ruibo, and Daxing Gao. "Innate Immunity and Tertiary Lymphoid Structures." Immunological Reviews 332, no. 1 (2025). https://doi.org/10.1111/imr.70052.

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ABSTRACTTertiary lymphoid structures (TLSs) are ectopic lymphoid tissues that form in response to chronic inflammation, such as in autoimmune diseases or cancer. Their presence has been increasingly recognized as a significant factor in determining patient prognosis and response to cancer treatments. The formation and development of TLSs are intricately linked to inflammatory cytokines and chemokines, which can be induced by the innate immune system. The innate immune system serves as the body's first line of defense against pathogens by producing cytokines and chemokines upon the detection of
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Yao, Zhiyuan, Gengchen Li, Di Pan, et al. "Roles and functions of tumor-infiltrating lymphocytes and tertiary lymphoid structures in gastric cancer progression." Frontiers in Immunology 16 (May 29, 2025). https://doi.org/10.3389/fimmu.2025.1595070.

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Gastric cancer (GC), a leading cause of cancer mortality, exhibits profound molecular heterogeneity and immunosuppressive tumor microenvironment (TME) features that limit therapeutic efficacy. This review elucidates the dual roles of tertiary lymphoid structures (TLS) and tumor-infiltrating lymphocytes (TILs) in GC progression. TLS, ectopic lymphoid organs formed under chronic inflammation, correlate with improved survival and immunotherapy sensitivity by fostering effector T/B cell interactions and antigen presentation. Conversely, immunosuppressive TME components like regulatory T cells (Tre
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Gao, Xinbo, Xiangqin Zhao, Xuesong Li, Jin Zhang, Hui Zhao, and Ying Ma. "Editorial: Tertiary lymphoid structures (TLS) in the tumor immune microenvironment." Frontiers in Immunology 16 (January 23, 2025). https://doi.org/10.3389/fimmu.2025.1555677.

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Wang, Qianyu, Wentao Zhong, Xiaofei Shen, et al. "Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer." npj Precision Oncology 8, no. 1 (2024). http://dx.doi.org/10.1038/s41698-024-00533-w.

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AbstractTertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was signif
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Sun, Guojuan, and Yi Liu. "Tertiary lymphoid structures in ovarian cancer." Frontiers in Immunology 15 (November 6, 2024). http://dx.doi.org/10.3389/fimmu.2024.1465516.

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Ovarian cancer (OC) is a significant cause of cancer-related mortality in women worldwide. Despite advances in treatment modalities, including surgery and chemotherapy, the overall prognosis for OC patients remains poor, particularly for patients with advanced or recurrent disease. Immunotherapy, particularly immune checkpoint blockade (ICB), has revolutionized cancer treatment in various malignancies but has shown limited efficacy in treating OC, which is primarily attributed to the immunologically. Tertiary lymphoid structures (TLSs), which are ectopic aggregates of immune cells, have emerge
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Gkegka, Anastasia G., Michael I. Koukourakis, Michael Katotomichelakis, and Alexandra Giatromanolaki. "Cancer Microenvironment Defines Tumor-Infiltrating Lymphocyte Density and Tertiary Lymphoid Structure Formation in Laryngeal Cancer." Head and Neck Pathology, December 31, 2022. http://dx.doi.org/10.1007/s12105-022-01517-7.

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Abstract Background The presence and activity of tumor-infiltrating lymphocytes (TILs) is a key parameter related to the antitumor immune response. A large number of studies reveal TIL density as a prognostic marker and predictor of response to radiotherapy, chemotherapy, and immunotherapy. Methods We examined the TIL and tertiary lymphoid structure TLS density in the invading front and inner tumor stroma, in a 33 squamous cell laryngeal carcinomas (LSCC) treated with laryngectomy. TIL and TLS densities were in parallel examined with markers of anaerobic metabolism, vascular density (VD), vasc
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Zhang, Yuyuan, Mengjun Xu, Yuqing Ren, et al. "Tertiary lymphoid structural heterogeneity determines tumour immunity and prospects for clinical application." Molecular Cancer 23, no. 1 (2024). http://dx.doi.org/10.1186/s12943-024-01980-6.

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AbstractTertiary lymphoid structures (TLS) are clusters of immune cells that resemble and function similarly to secondary lymphoid organs (SLOs). While TLS is generally associated with an anti-tumour immune response in most cancer types, it has also been observed to act as a pro-tumour immune response. The heterogeneity of TLS function is largely determined by the composition of tumour-infiltrating lymphocytes (TILs) and the balance of cell subsets within the tumour-associated TLS (TA-TLS). TA-TLS of varying maturity, density, and location may have opposing effects on tumour immunity. Higher m
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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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Liu, Zhonglong, Xiaoyan Meng, Xiao Tang, Weili Zou, and Yue He. "Intratumoral tertiary lymphoid structures promote patient survival and immunotherapy response in head neck squamous cell carcinoma." Cancer Immunology, Immunotherapy, December 8, 2022. http://dx.doi.org/10.1007/s00262-022-03310-5.

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AbstractTertiary lymphoid structures (TLSs) hold the potential role in the prediction of immunotherapy response in several clinical trials. TLSs in head neck squamous cell carcinoma (HNSCC) have been investigated through IHC analysis, whereas there is no TLS gene signature to evaluate the level of TLS neogenesis. We here proposed a TLS signature containing 13 chemokines and determined TLS-hi and TLS-low groups in HNSCC samples from The Cancer Genome Atlas. TLS-hi condition signified a better overall survival. A more inflamed immune infiltrative landscape was identified in the TLS-hi tumors cha
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Byers, Candice, Melissa Gill, Nicholas R. Kurtansky, et al. "Tertiary lymphoid structures accompanied by fibrillary matrix morphology impact anti-tumor immunity in basal cell carcinomas." Frontiers in Medicine 9 (October 27, 2022). http://dx.doi.org/10.3389/fmed.2022.981074.

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Tertiary lymphoid structures (TLS) are specialized lymphoid formations that serve as local repertoire of T- and B-cells at sites of chronic inflammation, autoimmunity, and cancer. While presence of TLS has been associated with improved response to immune checkpoint blockade therapies and overall outcomes in several cancers, its prognostic value in basal cell carcinoma (BCC) has not been investigated. Herein, we determined the prognostic impact of TLS by relating its prevalence and maturation with outcome measures of anti-tumor immunity, namely tumor infiltrating lymphocytes (TILs) and tumor ki
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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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