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Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non-small cell lung cancer. Although the detailed cellular and molecular mechanisms underlying these clinical associations have not been fully elucidated, growing preclinical and clinical studies are helping to elucidate the mechanisms at the basis of TLS formation, composition, and regulation of immune responses. However, a major challenge remains how to exploit TLS to enhance naïve and treatment-mediated antitumor immune responses. Here, we discuss the current understanding of tumor-associated TLS, preclinical models that can be used to study them, and potential therapeutic interventions to boost TLS formation, with a particular focus on lung cancer research.
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http://dx.doi.org/10.1158/0008-5472.CAN-23-3325 | DOI Listing |
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.
View Article and Find Full Text PDFUnlabelled: Juvenile idiopathic arthritis (JIA) is the most prevalent chronic inflammatory arthritis of childhood, yet the spatial organization in the synovium remains poorly understood. Here, we perform subcellular-resolution spatial transcriptomic profiling of synovial tissue from patients with active JIA. We identify diverse immune and stromal cell populations and reconstruct spatially defined cellular niches.
View Article and Find Full Text PDFGut
August 2025
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy
Background: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive biliary tract cancer with a poor prognosis and a complex tumour microenvironment (TME) that remains poorly understood.
Objective: This study aimed to investigate the phenotypic and molecular characteristics of B lymphocytes, their interactions with the TME and their prognostic implications.
Design: B-cell compartments in the tumour, peritumour, and peripheral blood of iCCA patients were analysed using multimodal single-cell technologies.