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Nachrichten, Termine, Experten
Researchers at Heinrich Heine University Düsseldorf (HHU) and University Hospital Düsseldorf (UKD) have succeeded in mapping the organisation of immune cells in human lymph nodes for the first time. The study was conducted in collaboration with the German Cancer Research Centre (DKFZ), the European Molecular Biology Laboratory (EMBL) in Heidelberg, the Berlin Institute of Health (BIH) at the Charité hospital Berlin and the University of Basel. They were able to show why lymph node architecture is progressively broken down in the case of malignant lymphomas. The researchers, led by Professor Dr Sascha Dietrich (UKD), have now published the results in the scientific journal Nature Cancer.
Lymph nodes are key control centres in the immune system and play an important role in defending the body against infections and tumours. For these processes to function properly, immune cells (B cells and T cells) must be organised in a precise spatial pattern in the lymph node tissue, for example in so-called B cell follicles and T cell zones. They are controlled by stromal cells (non-haematopoietic structural cells): They release messenger substances called chemokines, creating signals to guide the immune cells to their designated positions in the lymph node. In the case of B cell lymphomas, the internal structure of the lymph node tissue can be disturbed in very different ways, depending on the exact type of lymphoma: While the fundamental tissue structure remains intact in the case of slow-growing lymphomas such as follicular lymphoma (FL), aggressive lymphomas such as diffuse large B cell lymphoma (DLBCL) cause the tissue structure to break down completely. Why these typical growth patterns develop has been largely unclear to date.
In the study “Architectural principles of lymphoma-induced lymph node tissue remodeling”, the researchers coordinated by Professor Dietrich (Director of the Department of Haematology, Oncology and Clinical Immunology, UKD) have now succeeded in systematically mapping these processes in the human lymph node for the first time. By means of single-cell analyses and spatial tissue mapping, they were able to trace which factors lead to the progressive breakdown of the lymph node architecture in the case of lymphoma.
The data show: Stromal cells are the “architects” of the lymph node. The researchers were able to prove that central chemokine guiding signals in specialised stromal cells undergo fundamental changes over the course of lymphomagenesis, causing the progressive breakdown of the spatial structure of the lymph node. These stromal cell changes are reflected in the growth patterns of lymphomas – while there is a shift in the proportions of B cell follicles and T cell zones in FL, the areas remain spatially demarcated to a large extent; by contrast, there is widespread loss of important regulatory signals and thus tissue structure in DLBCL.
The study identified an inflammatory feedback loop as the driving mechanism: As part of the immune response in the tumour microenvironment, T cells produce inflammatory signalling proteins called interferons, which cause stromal cells to reprogramme their chemokine production: instead of structure-defining signals, inflammatory chemokines dominate, which in turn attract further inflammatory cells. The loss of lymph node organisation in lymphoma is thus not a passive effect of tumour growth, but rather actively driven by inflammation processes in the tumour microenvironment.
This reprogramming of stromal cells results in poorer patient survival rates. The study was able to demonstrate in large cohorts that a loss of structure-defining chemokines correlates with an unfavourable prognosis.
However, the findings also offer potential for new therapy approaches. “The study results show us that stabilisation of the stromal cells or targeted modulation of the inflammatory signals could be a promising new therapy approach,” says Professor Dietrich. “The findings could also help us identify new biomarkers in the future to enable early identification of aggressive disease progression,” he concludes.
The study took place within the framework of a national and international collaboration. In addition to Professor Dietrich and the Department of Haematology, Oncology and Clinical Immunology at UKD, leading partners included Dr Felix Czernilofsky (University Hospital Heidelberg), Dr Anna Mathioudaki (EMBL), Dr Lea Jopp-Saile (Max Delbrück Center for Molecular Medicine, Berlin), Professor Dr Simon Haas (BIH, Max Delbrück Center for Molecular Medicine, Berlin, Queen Mary University of London), Dr Daniel Hübschmann (DKFZ) and Professor Dr Judith Zaugg (EMBL and the University of Basel).
In Düsseldorf, Christina Schniederjohann (MSc), Dr Nora Liebers, Dr Peter-Martin Bruch, PD Dr Marc Seifert (all from the Department of Haematology, Oncology and Clinical Immunology) and Professor Dr Jörg Distler (Department of Rheumatology) were also involved.
Prof. Dr. Sascha Dietrich
Dr. rer. nat. Nicole Heise
“Architectural principles of lymphoma-induced lymph node tissue remodeling”
F. Czernilofzky, A. Mathoiudaki, L. Jopp-Saile, R. Lutz, D. Vonficht, X. Wang, C. Schiederjohann, H. Voehringer, T. Roider, M.-A. Baertsch, C. Rodemer, H. Löffler-Wirth, M. Grau, D. Fitzgerald, J. Mammen, J. Kosla, N. Liebers, P.-M. Bruch, D. Ordoñez-Rueda, A. Brobeil, G. Mechtersheimer, C. Pabst, C. Müller-Tidow, A. Trumpp, M. Seifert, F. Neumann, M. Heikenwälder, C. Benes, W. Huber, J. Distler, G. Lenz, H. Binder, R. Siebert, G. P. Nolan, M. Gerstung, J. B. Zaugg, D. Hübschmann, S. Haas, S. Dietrich. Nature Cancer 2026.
DOI: 10.1038/s43018-026-01136-z
https://www.nature.com/articles/s43018-026-01136-z
Professor Dr Sascha Dietrich (Director of the Department of Haematology, Oncology and Clinical Immun ...
Copyright: UKD
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Professor Dr Sascha Dietrich (Director of the Department of Haematology, Oncology and Clinical Immun ...
Copyright: UKD
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