Cancer Network Zurich – Cancer Biology Ph.D. Program

 
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University Hospital Zurich
Department of Oncology
 
Wagistrasse 14
8952 Schlieren
Phone +41-44-5563121, E-mail

Beffinger Michal

Main Field(s) of Research, Abstract
Non-melanoma skin cancer (NMSC) is the most common type of all tumours and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). One of the clinical treatment procedure involves topical application of Aldara, a cream containing 5% of imiquimod, a potent agonist of Toll-like receptor 7 (TLR7). This results in objective clinical responses in a proportion of BCC and pre-stage SCC patients. Aldara is a strong stimulant of immunological system although, despite wide usage, still little is known about direct mechanism of its action. Application of Aldara leads to strong inflammatory response, hyperproliferation of keratinocytes, induction of apoptosis in epidermal cells and infiltration of skin by granulocytes, lymphocytes and dendritic cells. Members of the latter group, plasmacytoid dendritic cells (pDCs), the main producers of type I interferon in humans, are considered as the most important cells in the tumour clearance. This is due to their high expression of TLR7 and ability to gain effector features upon stimulation with imiquimod. What is interesting, we and others could observe also TLR7-independent and even imiquimod-independent responses, which influence on final effect is not fully understood. In this project we are dissecting the mechanism of action of Aldara focusing on the TLR7-independent and type I interferon-independent reactions. For these reason we are identifying cell types and signalling cascades targeted by Aldara and how do they contribute to Aldara’s antitumoral activity.

Main Fields of Research, Keywords
Skin cancer, innate and adaptive immunity, Aldara.

Special Techniques and Equipment
In vivo experiments using murine model, primary cell culturing, FACS, real time quantitative PCR, fluorescence microscopy.