The impact of motility on lymphoma presentation and dissemination

运动性是免疫细胞的固有特征。恶性淋巴瘤起源于B或T细胞，通常与它们的起源细胞相似。最近，在细胞运动时发生的细胞内信号级联的表征方面取得了巨大的进展。有趣的是，促进运动的细胞内因子与T细胞受体途径的下游信号因子部分重叠。T细胞淋巴瘤尤其表现为运动性相关基因的体细胞突变。在这个项目中，我们希望将分子生物学和更多应用的临床病理学方法结合起来，以了解运动性在恶性淋巴瘤中的影响。我们以前在研究间变性大细胞淋巴瘤和经典霍奇金淋巴瘤细胞系的运动能力时观察到了惊人的差异。现在我们的目标是揭示为什么特定的淋巴瘤实体通过淋巴瘤细胞的运动性而不同，并为这种现象找到一个机制上的解释。我们特别想重点关注T细胞淋巴瘤、间变性大细胞淋巴瘤和血管免疫母细胞淋巴瘤，同时也会研究经典霍奇金淋巴瘤与其他B细胞淋巴瘤进行比较，以获得更全面的认识。我们将研究淋巴瘤细胞系和原代淋巴瘤细胞在Transwell小室、3D胶原胶、不同类型的微通道以及新鲜淋巴结/扁桃体的厚片中的运动性。我们将使用转基因和未转基因的细胞系，并将通过比较RNA测序和运动性和非运动性细胞群体的蛋白质组学技术来扩大我们的理解。从分子水平上更全面地了解恶性淋巴瘤的转移模式将有助于更好地了解这些疾病的病理生理和扩散模式，并可能成为指导预后和治疗的第一步。

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.