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

## TL;DR

The study shows how stromal cell changes in lymph nodes lead to loss of tissue structure in B cell lymphoma, impacting patient survival.

## Contribution

The paper reveals a tumor-reactive T cell-driven inflammatory feedback loop that reprograms stromal cells and disrupts lymph node architecture.

## Key findings

- Stromal cells are central to chemokine-driven lymphocyte organization in healthy lymph nodes.
- Tumor-reactive T cells trigger stromal remodeling and loss of chemokine gradients in follicular and diffuse large B cell lymphoma.
- Loss of homeostatic chemokines correlates with poor patient survival in lymphoma.

## 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.

Czernilofsky et al. identified factors that reprogram stromal cells into an inflammatory, dysfunctional state, leading to the structural disorganization of lymph nodes in B cell lymphoma at single-cell and spatial resolutions.