Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive B-cell non-Hodgkin lymphoma, often developing resistance to current treatments. Development and testing of new therapies is hampered by lack of good in vivo and in vitro models mimicking human disease. Here, we developed a lymphoma-on-chip model to investigate the tumor-supportive roles of lymph node stromal cells (LNSCs) - fibroblastic reticular cells (FRCs) and lymphatic endothelial cells (LECs) - in the DLBCL microenvironment. The model includes a tubular vessel lined with LECs surrounded by a hydrogel with DLBCL cells and FRCs. Our findings reveal that FRCs promote DLBCL survival and facilitate tumor cell migration towards lymphatic vessels. Moreover, we demonstrate that DLBCL cells increase permeability of lymphatic vessels, which is further enhanced in presence of FRCs. This lymphoma-on-chip model reveals the important role of LNSCs in DLBCL progression, and offers an innovative tool to study the DLBCL microenvironment and test potential therapeutic targets to improve patient outcomes.