The role of chemokine ligands and receptors in the dissemination of anaplastic large cell lymphoma

间变性大细胞淋巴瘤(ALCL)是一种表达CD30的T细胞淋巴瘤，与霍奇金淋巴瘤(HL)在形态上存在重叠。然而，在临床行为方面也观察到了重要的区别：ALCL通常表现为晚期，预后较差。然而，细胞微环境以及趋化因子及其相应的受体在HL中的作用已被广泛研究，但对ALCL的微环境以及趋化因子及其受体的表达知之甚少。趋化因子及其受体对白细胞的分布和运输具有重要影响。因此，本研究的目的是研究ALCL肿瘤和旁观者细胞上趋化因子配体和受体的表达，以及原代ALCL标本中微环境的组成，以更好地了解为ALCL肿瘤细胞提供生存优势的微环境。在原代ALCL样本中的发现随后可以应用于体外实验和在具有ALCL细胞系的本地人淋巴组织中的实验。趋化因子受体的表达将在ALCL细胞系中被调节，ALCL肿瘤细胞的行为将在与反应性旁观者细胞的共同培养中以及在迁移分析小室实验中被监测。此外，具有和不表达某些趋化因子受体的GFP标记的ALCL细胞株将被应用于人类淋巴组织的原代厚片上。通过这种分析，可以突出显示反应活跃的旁观者细胞，并使用活细胞成像显示所有标记细胞的反应、运动和相互作用。这些实验将有助于更好地了解ALCL肿瘤细胞在人类淋巴组织中的迁移行为和分布，以及它们与细胞微环境的相互作用。微环境相互作用和趋化因子表达的差异可能解释了与慢性粒细胞白血病相比不同的临床行为。此外，新的治疗方法在ALCL中的效果可以在视觉监测下在原发人体组织中进行测试。

Anaplastic large cell lymphoma (ALCL) is a CD30-expressing T-cell lymphoma, showing morphologic overlap with Hodgkin lymphoma (HL). However, important differences in clinical behavior have been observed: ALCL usually presents with advanced stage and has a worse prognosis. Whereas in HL the cellular microenvironment as well as the chemokines and their corresponding receptors, which together contribute to the composition of the microenvironment, have been extensively studied, very little is known about the microenvironment and the expression of chemokines and their receptors in ALCL. Chemokines and their receptors crucially impact the distribution and trafficking of leukocytes. Therefore, the aim of the present study is to characterize chemokine ligand and receptor expression on tumor and bystander cells in ALCL and to characterize the composition of the microenvironment in primary ALCL samples in order to better understand the microenvironmental niche which provides survival advantage for ALCL tumor cells. The findings in primary ALCL specimens can then be applied on in vitro experiments and experiments in native human lymphoid tissue with ALCL cell lines. Chemokine receptor expression will be modulated in ALCL cell lines and behavior of the ALCL tumor cells will be monitored in coculture with reactive bystander cells as well as in migration assay chamber experiments. Furthermore, GFP-labeled ALCL cell lines with and without expression of certain chemokine receptors will be applied onto primary thick slides of human lymphoid tissue. With this assay, additionally reactive bystander cells can be highlighted and the reactions, movements and interactions of all labeled cells will be visualized using live cell imaging. These experiments shall lead to a better understanding of the migration behavior and the distribution of ALCL tumor cells in human lymphoid tissue as well as their interaction with the cellular microenvironment. Differences in the microenvironmental interactions and chemokine expression may give an explanation of the differing clinical behavior when compared with cHL. Furthermore, the effects of novel therapeutic approaches in ALCL can be tested in primary human tissue under visual monitoring.