Architectural principles of lymphoma-induced lymph node tissue remodeling

Abstract: Organ function requires the organization of cells into higher order spatial units. However, the principles governing tissue architecture in health and disease remain poorly understood. Here, we utilized single-cell and spatial mapping to interrogate the mechanisms directing immune cell organization in human lymph nodes 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 lymph node stromal cells in chemokine-driven lymphocyte zonation and reveal an inflammatory feedback loop fueled by tumor-reactive T cells, triggering stromal remodeling, progressive loss of homeostatic chemokine gradients and tissue organization from non-malignant 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 lymph node organization and suggest how lymphoma-induced microenvironmental reprogramming drives loss of tissue organization. Data overview: Seurat object for mIF datamIF_seurat_final.rds Seurat object for scRNA-seq lymph node datascRNA_LN_stromal_cells.rds Seurat object for spatial transcriptomics/Xenium dataxenium_merged_seurat.rds Files related to Figure 3 - TCR-seq analysis202402_cd8_TCRobj_mapped.rds202402_TCRrepertoire.rds Files related to Figure 3 - SCENIC/GRN analysisGRN_90pt.rds Files related to Figure 3 - Seurat object for scRNA-seq co-culture dataCoCulture_DLBCL.rds Files related to Figure 4 - Scriabin analysisinteraction_potential.rdsmIF_knn_k6_pct_totalinteractions.csvmIF_knn_k6_pct_totalinteractions_rLN.csv Files related to Figure 5 - Bulk transcriptomicscibersortx_signature_matrix.txt