The annual International Immunity Day aims to raise awareness of the immune system and immunology research in fighting infections, autoimmune diseases and cancer. Immunologist Patrizia Stoetzner conducts research at the Medical University of Innsbruck and focuses mainly on dendritic cells – the so-called protective cells of the immune system.
Ms. Stoitzner, you are a professor of dermatology with a focus on tumor immunology and head of the laboratory for Langerhans cell research at the Dermatological Clinic in Innsbruck. What are Langerhans cells and what role do they play in our immune system?
Langerhans cells are a subset of dendritic cells. Star-shaped cells were discovered more than 150 years ago by Paul Langerhans, who originally thought they were nerve cells. In the 1980s, Nobel laureate Ralf Steinmann examined them more closely with the help of Austrian dermatologists and assigned them to dendritic cells and thus immune cells. Ralph even received a Nobel Prize for his research on dendritic cells and their importance in the immune system. Going back to Langerhans cells, these cells are found in the uppermost layer of the skin, the epidermis, which is why they are the first to come into contact with a pathogen or tumor. This makes them the protector cells of our immune system, as they are needed to trigger a successful immune response in the lymph nodes.
You are looking for skin cancer and new treatment approaches. Skin cancer is a prime example of the successful use of novel immunotherapies for cancer. why is that?
This is because melanoma is an immunogenic tumor, which means that we find many immune cells in tumor tissue, which unfortunately are usually malfunctioning there. However, these tumor-infiltrating immune cells, that is, immune cells migrating into the tumor tissue, can be reactivated against melanoma cells. Because of this profile, about 50 percent of skin cancer patients respond to treatment with what are known as immune checkpoint inhibitors, which can slow tumor growth for years, and also can bring about a permanent cure. Only recently can the importance of dendritic cells as checkpoint inhibitors driving the motor of response to immunotherapy be described. Among others, through our research, we were able to demonstrate that targeted activation and proliferation of dendritic cells directly in cancerous tissues together with checkpoint inhibitors contribute significantly to improving the response rate of melanoma immunotherapy. In the 1990s, when I started doing research, there was little chance of a cure for skin cancer because melanoma cells are relatively resistant to chemotherapy. That only changed ten years ago when the first immune checkpoint inhibitors were approved.
The immune system is very complex. However, can you paint a simple picture of how it works and how our bodies fight infections and other diseases?
Let’s stay with our largest organ, the skin. Here, the tumor grows in an environment full of immune cells. When melanocytes, the pigment cells of the skin, degenerate and develop into melanoma cells, Langerhans cells are present and capture parts of the tumor and transport them to the lymph nodes in order to present them to T cells – these are specialized immune cells. With this starting signal, dendritic cells activate a T-cell-mediated immune response against melanoma cells, which can be directly fought with cytokines and other messengers. T cells can divide further into subdivisions and become either killer T cells, which destroy damaged cells or viruses, or helper T cells, which in turn activate other immune cells, such as phagocytes or antibody-producing B cells. However, in some cases, this immune response can also go wrong, resulting in an excessive immune response that is also directed against healthy cells.
Will we ever fully understand the immune system?
This question is not easy to answer. I would say that we understand the immune system better and better and today already so well that we can develop new therapies and pursue new approaches with this knowledge and above all with ever better technologies. Much immunological information can be obtained from even the smallest patient samples. We understand better and better how dendritic cells interact with cancer cells, and how they trigger a T-cell response; We can better use this knowledge in the future to achieve better patient response in melanoma research, as mentioned earlier, through dendritic cell activation with immunotherapies.
What does the future hold?
The aging of society, changing living conditions and environmental pollution also cause an increase in cancer, but also in allergies. This presents an ongoing challenge to our immune system and, above all, to immunology research. Understanding of oncology has improved greatly in recent years. Immuno-oncology research has brought many innovations – mainly of a technological nature – which are also a constant point of focus at Med Uni Innsbruck. Here on campus, we take advantage of the short distances, researchers and clinicians meet in the corridor and exchange ideas. New results from the lab reach our patients directly and quickly. Thus we give a prime example of what is called translational research. A new multiplex imaging platform will soon be on campus, where tumor sections will enable the use of more than 50 markers to analyze the interaction of immune cells with tumor cells in more detail and directly in tissues. In order to develop innovative animal-free model systems, I am also working with colleagues at the Medical University of Innsbruck, for example with Michael Oserlechner and Doris Welflingsder on 3D printed models of skin and melanoma.
*) Immune checkpoint inhibitors are antibodies developed to activate the immune system: they target the body’s “brake” in the immune system, thus preventing cancer cells from dampening the immune response.
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Patricia Stoetzner, who was born in Vorarlberg, completed a degree in Microbiology and a PhD in Immunology from the Leopold-Franzen-University of Innsbruck and qualified in 2008 in the subject of Immunology. Since 2007, she has headed the Langerhans Cell Research Laboratory at the University Clinic for Dermatology and Allergy, where new and improved therapeutic approaches are being developed to immunize the organism against tumors. Stoitzner is also coordinator of the largest PhD program (Molecular and Cellular Biology of Disease / MCBD) at the Medical University of Innsbruck.
Rückfragehinweis: Medizinische Universität Innsbruck Public Relations und Medien Doris Heidegger Innrain 52, 6020 Innsbruck, Austria Telefon: +43 512 9003 70083 [email protected] www.i-med.ac.at
