Journal Article

DKFZ-2026-00677

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma.

Czernilofsky, F. ; Mathioudaki, A. (First author)DKFZ* ; Jopp-Saile, L. (First author)DKFZ* ; Lutz, R.DKFZ* ; Vonficht, D.DKFZ* ; Wang, X. ; Schniederjohann, C. ; Voehringer, H. ; Roider, T. ; Baertsch, M.-A. ; Rodemer, C. ; Löffler-Wirth, H. ; Grau, M. ; Fitzgerald, D. ; Mammen, J. ; Kosla, J.DKFZ* ; Liebers, N. ; Bruch, P.-M. ; Ordoñez-Rueda, D. ; Brobeil, A. ; Mechtersheimer, G. ; Pabst, C. ; Müller-Tidow, C. ; Trumpp, A.DKFZ* ; Seifert, M. ; Neumann, F. ; Heikenwälder, M.DKFZ* ; Benes, V. ; Huber, W. ; Distler, J. ; Lenz, G. ; Binder, H. ; Siebert, R. ; Nolan, G. P. ; Gerstung, M.DKFZ* ; Zaugg, J. B. ; Hübschmann, D. (Last author)DKFZ* ; Haas, S.DKFZ* ; Dietrich, S.

2026
Nature Research London

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.

Note: #EA:B450#EA:A010#LA:W015# / #DKTKZFB26# / #NCTZFB26# / 2026 Mar;7(3):538-552

---

Contributing Institute(s):

1. Künstl. Intelligenz in der Onkologie (B450)
2. A010 Stammzellen und Krebs (A010)
3. Chronische Entzündung und Krebs (D440)
4. Koordinierungsstelle NCT Heidelberg (HD02)
5. Innovations- und Service-Unit für Bioinformatik und Präzisionsmedizin (W015)
6. DKTK HD zentral (HD01)
7. DKTK Koordinierungsstelle Berlin (BE01)

Research Program(s):

1. 319H - Addenda (POF4-319H) (POF4-319H)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---