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Research focus of the Legler group

Overview

It is the the immune system that protects the human body against invading pathogens, toxins and abnormal cancer cell proliferation. Many different specialised cell types constitute the immune system. The primary function of immune cells is to identify, engage and remove pathogens and cancer cells. Part of the efficiency of the immune system relies on its ability to “learn” from previous invasion in order to display a swifter response to subsequent attacks from the same pathogens. Immune cells also undergo a radical selection process and are kept in check to prevent autoimmunity. An essential and common feature of immune cells is their high mobility. To ensure rapid detection of pathogens or abnormal cells, immune cells constantly patrol the human body.


Dendritic cells and their role in launching a natural immune response against pathogens and cancer cells

Dendritic cells can be viewed as the sentinels of the immune system, as they constantly sample tissues for invading pathogens. Upon pathogen encounter, dendritic cells start expressing a cell surface receptor (CCR7) that recognises chemokines, which are specific attractant molecules. Chemokines then guide the activated, antigen-bearing dendritic cells through tissues towards lymph vessels and finally to the closest draining lymph node. Once in lymph nodes, activated dendritic cells organise the immune response against the pathogen or against cancer cells they have been activated by, and eventually contribute to establish the immunological memory. Hence, directed migration of dendritic cells is a fundamental step in a proper immune response. Different signals, which lead to the activation and migration of immune cells, determine the quality and efficiency of the initiated immune response. We investigate the molecular mechanisms that enable the various cells of the immune system to recognise and respond to chemokines that “show them the way”. One aspect of our research is to identify new molecules and signalling pathways that can specifically regulate the migration and activation of immune cells. We have for instance previously demonstrated that prostaglandin E2, a messenger molecule in inflammation, profoundly influences the activation of dendritic cells and thereby has a tremendous impact on the success of the immune response. We are currently expanding these results by trying to understand the molecular mechanisms by which prostaglandin E2 and additional inflammatory mediators regulate activation and migration of dendritic cells.


Migration of cancer cells and metastasis formation

Cancer cells can also express the chemokine receptor CCR7, which is normally found at the surface of immune cells. Because CCR7 expressing cancer cells respond to the same chemokines as the immune cells, they too migrate to lymph nodes and other organs of the lymphatic system, where they form metastasis. We investigate what are the signals that trigger expression of chemokine receptors at the surface of cancer cells and how cancer cell migration is regulated. We are especially interested in the differences between the migration phenotype of cancer and immune cells. The aim of this research is to contribute to the development of new therapeutic strategies, focused on preventing cancer cells to follow the path of immune cells to the lymphatic system.