Group Legler

Research topics

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Dendritic cells: key players in launching natural immune responses against pathogens and tumors

Dendritic cells (DCs) are professional antigen-presenting cells operating as sentinels of the immune system. Upon pathogen (e.g. viruses, bacteria, tumor cells) encountering, DCs take-up and process antigens, produce cytokines and chemokines to activate and recruit other immune cells. Activated, antigen-loaded DCs then migrate to the draining lymph node to launch and orchestrate the specific immune response and the immunological memory. In clinical trials, DCs of cancer patients are loaded with tumor-specific antigens to initiate a natural immune response in where DCs activate the patient’s own cytotoxic T lymphocytes to kill cancer cells. Cell migration is guided by chemokines and fundamentally important to initiate immune responses. The chemokines CCL19 and CCL21 are constitutively expressed in lymphoid organs and recruit antigen-bearing DCs and lymphocytes via its cognate chemokine receptor CCR7. Signals initiating DC maturation and migration determine the outcome of an adaptive immune response. Recent advances point to a crucial role of inflammatory mediators, such as prostaglandin E2, in modulating DC functions. We are currently studying molecular mechanisms by which prostaglandin E2 regulates DC functions and migration, and consequently shapes adaptive immune responses against infection and cancer.

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Cancer cell migration – metastasis formation

The chemokine receptor CCR7 is not only responsible for dendritic cell and lymphocyte migration but is also expressed on a variety of tumor cells. Cancer cells expressing CCR7 respond to the chemokines CCL19 and CCL21 to metastasize to draining lymph nodes and other lymphoid organs. We are investigating how the expression of CCR7 is regulated and how cancer cells migrate in response to chemokines.

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CCR7-mediated signaling and cell migration

The main function of chemokines is to navigate cell migration. However, chemokines also fulfill other functions. For instance, chemokines can provide cell survival and cell proliferation signals or are involved in endocytosis. We are interested in different signaling pathways elicited by CCR7 in DCs, lymphocytes and cancer cells. Moreover, we aim to identify novel signaling motifs and interaction partners of CCR7 to understand and interfere with these signaling pathways. Understanding how chemokine receptors transmit signals resulting in immune cell and cancer cell migration/activation and identifying ways to modulate chemotaxis or to silence receptor signaling is of great interest for future therapeutic strategies.