Influence of the Lymph Node Stromal Microenvironment on the Development of Malignant B Lymphocytes

In lymphoma pathogenesis, homeostatic chemokine receptors and their cognate ligands gain particular interest because of their ability to organize lymphoid structures. Thus, the crosstalk between tumor cells and their stromal microenvironment via these engagements could give rise to the infiltration and subsequent proliferation of malignant lymphocytes. However, a detailed characterization of the molecular mechanisms involved in lymphoma cell survival is warranted. More specifically, it remains unclear which cellular stromal elements collaborate with lymphoma cells and how the tumor cells get access to their putative anti-apoptotic and pro-survival niche.

Here, we apply an oncogene-driven transgenic mouse model, the Eμ-Myc mouse strain, which mimics an aggressive type of B cell lymphoma. Upon adaptive transfer, Eμ-Myc tumor cells home to the lymph node paracortex, where they find a growth promoting microenvironment. To better understand the molecular interactions between benign or malignant lymphoid cells and stromal cells, we focus in this project on lymphoma-induced changes in the stromal compartment, as determined by transcriptional profiling. Furthermore, we aim to identify the influence of a tumor-induced alteration of the vasculature on tumor cell trafficking and the formation of a pro-survival niche for lymphoma B cells.