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<p>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.</p>

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Reprogramming of stroma-derived chemokine networks drives the loss of tissue organization in nodal B cell lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月25日

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  • Felix Czernilofsky,
  • Anna Mathioudaki,
  • Lea Jopp-Saile,
  • Raphael Lutz,
  • Dominik Vonficht,
  • Xi Wang,
  • Christina Schniederjohann,
  • Harald Voehringer,
  • Tobias Roider,
  • Marc-Andrea Baertsch,
  • Claus Rodemer,
  • Henry Löffler-Wirth,
  • Michael Grau,
  • Donnacha Fitzgerald,
  • Johannes Mammen,
  • Jan Kosla,
  • Nora Liebers,
  • Peter-Martin Bruch,
  • Diana Ordoñez-Rueda,
  • Alexander Brobeil,
  • Gunhild Mechtersheimer,
  • Caroline Pabst,
  • Carsten Müller-Tidow,
  • Andreas Trumpp,
  • Marc Seifert,
  • Frank Neumann,
  • Mathias Heikenwälder,
  • Vladimir Benes,
  • Wolfgang Huber,
  • Jörg Distler,
  • Georg Lenz,
  • Hans Binder,
  • Reiner Siebert,
  • Garry P. Nolan,
  • Moritz Gerstung,
  • Judith B. Zaugg,
  • Daniel Hübschmann,
  • Simon Haas,
  • Sascha Dietrich

摘要

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.