Tertiary lymphoid structures (TLS) are ectopic lymphoid formations that form within nonlymphoid tissue. They share structural and functional characteristics with secondary lymphoid structures such as lymph nodes and can contain B-cell follicles and germinal centers surrounded by a T-cell region. TLS have been described in several types of cancers and are usually associated with positive patient outcomes. However, TLS differ vastly in cellular composition and location within tissue types. In this review, we discuss factors confounding the interpretation of the evidence for a prognostic role for TLS in cancer and frame these factors in the context of translation to regular clinical use.
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http://dx.doi.org/10.1038/s41423-020-0457-0 | DOI Listing |
J Transl Med
January 2025
Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in China, commonly associated with undifferentiated cell types and Epstein-Barr virus (EBV) infection. The presence of intense lymphocytic infiltration and elevated expression of programmed cell death ligand 1(PD-L1) in NPC highlights its potential for immunotherapy, yet current treatment outcomes remain suboptimal. In this review, we explore the tumor microenvironment of NPC to better understand the mechanisms of resistance to immunotherapy, evaluate current therapeutic strategies, and pinpoint emerging targets, such as tertiary lymphoid structures (TLSs), that could enhance treatment outcomes and prognostic accuracy.
View Article and Find Full Text PDFNat Rev Urol
January 2025
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
Spatial transcriptomics has emerged as a powerful tool for discerning the heterogeneity of the tumour microenvironment across various cancers, including renal cell carcinoma (RCC). Spatial transcriptomics-based studies conducted in clear-cell RCC (the only RCC subtype studied using this technique to date) have given insights into spatial interactions within this disease. These insights include the role of epithelial-to-mesenchymal transitioning, revealing proximity-dependent interactions between tumour cells, fibroblasts, interleukin-2-expressing macrophages and hyalinized regions.
View Article and Find Full Text PDFNat Cancer
January 2025
Department of Hematopoietic Biology and Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Immune checkpoint inhibitors can lead to 'exceptional', durable responses in a subset of persons. However, the molecular basis of exceptional response (ER) to immunotherapy in metastatic clear cell renal cell carcinoma (mccRCC) has not been well characterized. Here we analyzed pretherapy genomic and transcriptomic data in treatment-naive persons with mccRCC treated with standard-of-care immunotherapies: (1) combination of programmed cell death protein and ligand 1 (PD1/PDL1) and cytotoxic T lymphocyte-associated protein 4 inhibitors (IO/IO) or (2) combination of PD1/PDL1 and vascular endothelial growth factor (VEGF) receptor inhibitors (IO/VEGF).
View Article and Find Full Text PDFSignal Transduct Target Ther
January 2025
The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
The mucosal immune system, as the most extensive peripheral immune network, serves as the frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion and establishing immune tolerance. A comprehensive understanding of mucosal immunity is essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing the overall impact on the body.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Moscow 121552, Russia.
Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization.
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