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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: |
Czernilofsky, Felix, Mathioudaki, Anna  ORCID: https://orcid.org/0000-0003-4617-7015, Jopp-Saile, Lea ORCID: https://orcid.org/0000-0002-7032-3003, Lutz, Raphael, Vonficht, Dominik, Wang, Xi ORCID: https://orcid.org/0000-0002-7572-6354, Schniederjohann, Christina, Voehringer, Harald, Roider, Tobias, Baertsch, Marc-Andrea ORCID: https://orcid.org/0000-0002-4000-6904, Rodemer, Claus, Löffler-Wirth, Henry, Grau, Michael, Fitzgerald, Donnacha ORCID: https://orcid.org/0000-0003-4927-7484, Mammen, Johannes, Kosla, Jan, Liebers, Nora ORCID: https://orcid.org/0009-0008-3887-9416, Bruch, Peter-Martin ORCID: https://orcid.org/0000-0002-9992-3109, Ordoñez-Rueda, Diana, Brobeil, Alexander, Mechtersheimer, Gunhild, Pabst, Caroline ORCID: https://orcid.org/0000-0001-9716-5909, Müller-Tidow, Carsten ORCID: https://orcid.org/0000-0002-7166-5232, Trumpp, Andreas ORCID: https://orcid.org/0000-0002-6212-3466, Seifert, Marc ORCID: https://orcid.org/0000-0001-9453-369X, Neumann, Frank, Heikenwälder, Mathias ORCID: https://orcid.org/0000-0002-3135-2274, Benes, Vladimir ORCID: https://orcid.org/0000-0002-0352-2547, Huber, Wolfgang, Distler, Jörg ORCID: https://orcid.org/0000-0001-7408-9333, Lenz, Georg ORCID: https://orcid.org/0000-0002-4728-1693, Binder, Hans ORCID: https://orcid.org/0000-0002-2242-4678, Siebert, Reiner, Nolan, Garry P. ORCID: https://orcid.org/0000-0002-8862-9043, Gerstung, Moritz ORCID: https://orcid.org/0000-0001-6709-963X, Zaugg, Judith B. ORCID: https://orcid.org/0000-0001-8324-4040, Hübschmann, Daniel ORCID: https://orcid.org/0000-0002-6041-7049, Haas, Simon ORCID: https://orcid.org/0000-0001-9227-2051 and Dietrich, Sascha ORCID: https://orcid.org/0000-0002-0648-1832
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| 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 |
| Related to: |
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