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| Item Type: | Article |
|---|---|
| Title: | Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma |
| Creators Name: | Czernilofsky, Felix, Mathioudaki, Anna, Jopp-Saile, Lea, Lutz, Raphael, Vonficht, Dominik, Wang, Xi, Schniederjohann, Christina, Voehringer, Harald, Roider, Tobias, Baertsch, Marc-Andrea, Rodemer, Claus, Löffler-Wirth, Henry, Grau, Michael, Fitzgerald, Donnacha, Mammen, Johannes, Kosla, Jan, Liebers, Nora, Bruch, Peter-Martin, Ordoñez-Rueda, Diana, Brobeil, Alexander, Mechtersheimer, Gunhild, Pabst, Caroline, Müller-Tidow, Carsten, Trumpp, Andreas, Seifert, Marc, Neumann, Frank, Heikenwälder, Mathias, Benes, Vladimir, Huber, Wolfgang, Distler, Jörg, Lenz, Georg, Binder, Hans, Siebert, Reiner, Nolan, Garry P., Gerstung, Moritz, Zaugg, Judith B., Hübschmann, Daniel, Haas, Simon and Dietrich, Sascha |
| Abstract: | Lymph node (LN) function requires the organization of cells into higher-order spatial units. However, the principles governing LN architecture in health and disease remain poorly understood. Here, we used single-cell and spatial mapping to investigate the mechanisms directing immune cell organization in human LNs and its disruption in architecturally distinct lymphoma entities: indolent follicular lymphoma (FL) and aggressive diffuse large B cell lymphoma (DLBCL). Our data substantiate the central role of LN-resident stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells that triggers stromal remodeling, progressive loss of homeostatic chemokine gradients, and tissue disorganization from a non-malignant state to FL and DLBCL. Loss of homeostatic chemokines was associated with adverse patient survival, identifying the underlying architectural rearrangement as a key event during lymphomagenesis. Collectively, our results highlight the principles of LN organization and suggest how lymphoma-induced microenvironmental reprogramming drives the loss of tissue organization. |
| Keywords: | Chemokines, Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Lymph Nodes, Single-Cell Analysis, Stromal Cells, Tumor Microenvironment |
| Source: | Nature Cancer |
| ISSN: | 2662-1347 |
| Publisher: | Springer Nature |
| Volume: | 7 |
| Number: | 3 |
| Page Range: | 538-552 |
| Date: | March 2026 |
| Official Publication: | https://doi.org/10.1038/s43018-026-01136-z |
| PubMed: | View item in PubMed |
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