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

点击翻译按钮获取中文摘要

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.