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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 showed that TLS can be induced by therapeutic interventions during cancer treatments. Thus, the evaluation of TLS maturity and the therapeutic interventions that induce its formation are critical issues in current TLS research. In this review, we aim to provide a comprehensive summary of the existing classifications for TLS maturity and therapeutic strategies capable of inducing its formation in tumors.
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http://dx.doi.org/10.3389/fimmu.2024.1369626 | DOI Listing |
Mol Carcinog
September 2025
Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
B cells located in tertiary lymphoid structures (TLSs) may undergo clonal expansion, somatic hypermutation, isotype switching, and tumor-specific antibody production, suggesting that antibody-producing plasma cells may be involved in antitumor immunity. This study used a combination of single-cell sequencing (five samples from our center, and four samples from PRJNA662018) and spatial transcriptome (one sample from our center, and four samples from GSE169379) research methods to investigate the relationship between TLSs and the immunoglobulin repertoire in muscle invasive bladder cancer (MIBC). 405 patients with MIBC from TCGA and 348 patients with metastatic urothelial carcinoma on PD-L1 inhibitor treatment from the IMvigor210 trial were included in this study.
View Article and Find Full Text PDFFront Immunol
September 2025
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Background: Tertiary lymphoid structures (TLSs) are linked to prognosis in esophageal squamous cell carcinoma (ESCC), but whether the distribution, abundance, and maturity of TLSs affect therapeutic efficacy and prognosis in ESCC treated with neoadjuvant chemoradiotherapy plus immunotherapy (NRCI) remains unclear. We explored TLS characteristics and correlated them with patient survival.
Methods: A total of 157 resectable ESCC patients treated with neoadjuvant therapy between September 2020 and May 2023 were divided into NRCI (n=49) and neoadjuvant chemoimmunotherapy (NCI, n=108) groups.
Immunol Rev
September 2025
Laboratory of Barrier Immunity, Division of Molecular Hematology, Department of Laboratory Medicine, Faculty of Medicine, Lund University, Lund, Sweden.
The skin is the outermost organ that serves as the host's live, microbiota-inhabited physical border, evolved to cope with continuous confrontation by a wide variety of environmental elements. This dynamic borderline is prone to injury and damage. Therefore, to deliver on the critical demands for protection, skin is tightly associated with innate and adaptive defense mechanisms that ensure homeostatic tissue barrier integrity.
View Article and Find Full Text PDFJ Immunol
September 2025
Research and Medical Affairs, Amgen Inc, Thousand Oaks, CA, United States.
The Feline McDonough sarcoma-like tyrosine kinase 3 (FLT3)/FLT3 ligand (FLT3L) pathway is associated with pathogenesis of several autoimmune diseases, including Sjögren's. Inflammatory signals increase FLT3L levels; FLT3L signaling promotes further inflammation through the differentiation, function, and survival of immune cells, including dendritic cells (DCs), monocytes, and B cells. Patients with Sjögren's have elevated FLT3L levels, increased infiltration of DCs, macrophages, and B cells into salivary glands and tertiary lymphoid structures (TLS).
View Article and Find Full Text PDFNat Immunol
September 2025
Cancer and Blood Disorders Institute, Institute for Fundamental Biomedical Research, and Department of Surgery, Johns Hopkins All Children's Hospital, and Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, St. Petersburg, FL, USA.
B cell-rich tertiary lymphoid structures (TLS) are associated with favorable prognosis and positive response to immunotherapy in cancer. Here we show that simultaneous activation of innate immune effectors, STING and lymphotoxin-β receptor (LTβR), results in CD8 T cell-dependent tumor suppression while inducing high endothelial venule development and germinal center-like B cell responses in tumors to generate functional TLS in a T cell-dependent manner. In a neoadjuvant setting, activation of STING and LTβR by their agonists effectively immunized mice against tumor recurrence, leading to long-term survival.
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