The impact of motility on lymphoma presentation and dissemination

• Applicant: Professorin Dr. Sylvia Hartmann
• Subject Area: Pathology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 452315700

Motility is an intrinsic feature of immune cells. Malignant lymphomas derive from B or T cells and usually resemble their cells of origin. Recently, tremendous advances in the characterization of intracellular signaling cascades, that take place when a cell moves, were achieved. Interestingly, the intracellular factors that promote motility partly overlap with downstream signaling factors of the T-cell receptor pathway. T-cell lymphomas in particular show somatic mutations in motility-related genes. In this project we want to bring together molecular biological and more applied clinicopathological approaches to learn about the impact of motility in malignant lymphomas. We previously observed surprising differences when studying the motility of anaplastic large cell lymphoma and classical Hodgkin lymphoma cell lines. Now we aim to reveal why specific lymphoma entities differ from each other by the motility of the lymphoma cells and to find a mechanistic explanation for this phenomenon. We particularly want to focus on the T-cell lymphomas anaplastic large cell lymphoma and angioimmunoblastic lymphoma, but will also study classical Hodgkin lymphoma and other B-cell lymphomas for comparison to obtain a more comprehensive understanding. We will study the motility of lymphoma cell lines and primary lymphoma cells in transwell chambers, 3D collagen gels, different types of microchannels as well as in thick slices of fresh lymph nodes/tonsils. We will use genetically modified and unmodified cell lines and will enlarge our understanding by comparative RNA sequencing and proteomic technologies of motile and non-motile cell populations. A more comprehensive molecular understanding of the migration patterns of malignant lymphomas will contribute to a better understanding of the pathophysiology and dissemination patterns of these diseases and may be a first step implying motility in prognosis and treatment.

• DFG Programme: Research Grants