P1218: A REPROGRAMMING OF THE LYMPH NODE MICROENVIRONMENT UNDERLIES LOSS OF COMPARTMENTALISATION IN AGGRESSIVE LYMPHOMAS

• DOI: 10.1097/01.hs9.0000971768.77250.1d
• Publication Date: 2023-08-09T14:36:12Z
• Authors: Anna Mathioudaki; Felix Czernilofsky; Lea Jopp-Saile; Raphael Lutz; Dominik Vonflicht; XI Wang; Marc-A. Baertsch; Harald Vohringer; Tobias Roider; Johannes Mammen; Diana Ordonez-Rueda; Caroline Pabst; Wolfgang Huber; Andreas Trumpp; Carsten Müller-T...; Gary P. Nolan; Vladimir Benes; Judith B. Zaugg; Daniel Hübschmann; Simon Haas; Sascha Dietrich
• Keywords: Follicular lymphoma

Topic: 20. Lymphoma Biology & Translational Research Background: The function of lymph nodes depends on the coordinated structure defined by node stromal cells (LNSC), which consist endothelial as well chemokine-secreting mesenchymal cells. In B cell non-Hodgkin lymphoma (B-NHL), LN is disrupted, indicating that LNSCs play a crucial role within tumor microenvironment (TME). Nevertheless, molecular mechanisms reprogramming in B-NHL are not comprehended. Aims: Here, we studied TME order to address long-standing question why some lymphomas grow more organized manner, whereas others diffusely. Methods: To understand pathomechanisms aggressive lymphomas, analyzed primary human samples different growth patterns (follicular lymphoma, n = 9; diffused large DLBCL, 11) non-malignant controls (reactive nodes, n=7) combining single-cell transcriptomics (scRNA-seq) with multiplexed immunofluorescence imaging (CODEX) together vitro co-culture models. Results: Spatial single-cell-resolved analysis allowed fine mapping neighborhoods and compositional changes lymphomagenesis, including disruption vasculature expansion These associated were characterized distinct fibrotic inflammatory signatures dysregulated chemokine gradients, suggesting phenotypic switch from structural organizers an state. silico cell-cell attraction revealed detected sufficient explain loss organization DLBCL. Furthermore, assays using patient-derived validated lymphocyte-dependent secretome cells, elevated expression chemokines. findings further corroborated independent patient cohort, where showed adequately reflects extent LN’s B-NHL. Summary/Conclusion: Altogether, our provide valuable insights into non-hematopoietic lay foundation for understanding remodeling at niche-level.Keywords: Diffuse Non-Hodgkin’s Microenvironment, Follicular