Tertiary lymphoid structures (TLS) are inducible ectopic lymphoid aggregates, which form in response to various inflammatory situations, including cancer. TLS are notably composed of B lymphocytes, T lymphocytes, mature dendritic cells and other key players such as high endothelial venules. Furthermore, TLS can present different levels of organization and maturation, from simple T/B lymphocyte aggregates to authentic mature B cell follicles with germinal centers adjacent to T cell rich areas. While over the past decade, TLS may have been associated with a favorable prognosis in various cancers, the year 2022 was marked by the first prospective trial (PEMBROSARC) that reported the interest of TLS as predictive biomarkers of pembrolizumab efficacy for the treatment of soft-tissue sarcomas. All along this review, we will first address the molecular and cellular bases of TLS as well as the different strategies for identifying them in clinical practice, then discuss the prognostic/predictive impact of their presence and finally, we will elaborate on the current limitations and perspectives in translational research.
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http://dx.doi.org/10.1016/j.bulcan.2023.04.010 | DOI Listing |
The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers.
View Article and Find Full Text PDFTransl Lung Cancer Res
December 2024
Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Background: Differences in the immune microenvironment and responses to immunotherapy may exist between primary non-small cell lung cancer (NSCLC) and brain metastases (BMs). This study aimed to investigate discrepancies in programmed death-ligand 1 (PD-L1) expression, tumor-infiltrating lymphocytes (TILs), tertiary lymphoid structures (TLS), and tumor mutational burden (TMB) between matched BMs and primary tumors (PTs) in NSCLC.
Methods: Twenty-six pairs of surgically resected BMs and corresponding PTs from NSCLC patients were collected.
Transl Lung Cancer Res
December 2024
Department of Pathology, Molecular Pathology Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Background: The tumor immune microenvironment of anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinoma (LUAD) stratified by ALK fusion variants is poorly pictured. Hence, in this study, we aim to explore the immune heterogeneity of ALK LUAD across different ALK fusion variants and further investigate their significance on clinical prognosis.
Methods: A retrospective analysis was conducted on ALK LUAD patients (N=68).
Single-cell RNA sequencing studies have revealed the heterogeneity of cell states present in the rheumatoid arthritis (RA) synovium. However, it remains unclear how these cell types interact with one another and how synovial microenvironments shape observed cell states. Here, we use spatial transcriptomics (ST) to define stable microenvironments across eight synovial tissue samples from six RA patients and characterize the cellular composition of ectopic lymphoid structures (ELS).
View Article and Find Full Text PDFBMC Cancer
January 2025
Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Background: There is still no consensus regarding the correlation between TLS and the prognosis of lung cancer patients. This meta-analysis aimed to investigate the association between TLS and prognosis in patients with lung cancer. In addition, the prognostic value of TLS for the efficacy of immunotherapy was also studied.
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