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Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions.
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http://dx.doi.org/10.1016/j.it.2014.09.006 | DOI Listing |
Immunity
March 2025
Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:
Anti-vascular endothelial growth factor (VEGF) treatment has shown clinical activity together with immune checkpoint blockade (ICB), but the exact mechanism is not known. We show that VEGF blockade in combination with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) + anti-programmed death-ligand 1 (PD-L1) in cholangiocarcinoma (CCA) potentiated a multimodal mechanism dependent on B cell activating factor (BAFF), leading to a proinflammatory B cell response. It led to a BAFF- and interleukin (IL)-12-dependent expansion and rewiring of T regulatory cells (Tregs) toward an anti-tumor T helper-1 (Th-1)-like fragile state.
View Article and Find Full Text PDFFront Immunol
March 2025
Research Laboratory Center, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
Background: Breast cancer, a highly prevalent global cancer, poses significant challenges, especially in advanced stages. Prognostic models are crucial to enhance patient outcomes. Tertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with better prognostic outcomes.
View Article and Find Full Text PDFJ Exp Clin Cancer Res
March 2025
Department of Thyroid Surgery, Clinical Research Center for Thyroid Diseases of Yunnan Province, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
Objective: Active surveillance (AS) offers a viable alternative to surgical intervention for the management of indolent papillary thyroid carcinoma (PTC), helping to minimize the incidence of unnecessary treatment. However, the broader adoption of AS is hindered by the need for more reliable diagnostic markers. This study aimed to identify the differences between indolent and progressive PTC and find new targets for biomarker development and therapeutic strategies.
View Article and Find Full Text PDFJ Transl Med
March 2025
Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive cancers, with rising incidence and limited responsiveness to immunotherapy due to its highly suppressive tumor microenvironment (TME). Tertiary lymphoid structures (TLS), ectopic formation structures of immune cells, are linked to better prognosis and improved immunotherapy responses in PDAC. Understanding TLS's role in PDAC could enhance immunotherapy effectiveness.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
March 2025
Inflammation Research Network, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Crohn's disease (CD) is a chronic inflammatory bowel disease which also encompasses significant alterations of the mesenteric lymphatic system. Whether these changes are a mere consequence of, or directly contribute to the inflammation is unknown. Here we characterized the spatial and temporal development of these events in the TNF mouse, which develops CD-like ileitis and significant mesenteric lymphatic alterations.
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