How do chloroplasts prevent cancer

Potential adjusting screw for more effective cancer immunotherapies

The focus is on the messenger substance interleukin-33 (IL-33). If the production of IL-33 in regulatory T cells in the tumor and in the immediate vicinity of the tumor is suppressed, tumor growth is reduced and immunotherapies show increased effectiveness in experimental models.

Understanding the mechanism could provide an approach to developing new immunotherapeutic approaches. The results of the investigation were published in the journal "Nature Immunology" (www.nature.com, DOI 10.1038 / s41590-019-0555-2).

Despite impressive clinical successes, cancer immunotherapies are ineffective in many patients. Regulatory T cells, so-called Tregs, which can inhibit an immune response directed against the tumor, play an important role here. Scientists from the Biomedical Research Foundation of the Athens Academy, the Institute for Clinical Chemistry and Laboratory Medicine of the University Hospital Carl Gustav Carus Dresden and the National Center for Tumor Diseases Dresden (NCT / UCC) have now shown that a special messenger substance occurring in the Tregs - interleukin-33 - is a possible adjustment screw for the function of the cells and for a better effectiveness of immunotherapies in the future.

Regulatory T cells accumulate to a particular degree in and around the tumor. They do an anti-inflammatory job by calming down the immune system. This actually positive property for preventing excessive immune reactions is counterproductive in the tumor and the direct tumor environment: Here the immune system should be highly active in order to fight the tumor. The excess Tregs promote tumor growth and in many cases hinder the effectiveness of tumor immunotherapy.

In contrast to Tregs in other regions of the body, regulatory T cells in the tumor and the immediate tumor environment have a particularly high content of the messenger substance interleukin-33 (IL-33). As the researchers have now been able to show on the basis of various experimental models, a blockade of IL-33 production reduces the inhibitory properties of the Tregs and thus leads to a decline in tumor growth and better effectiveness of immunotherapies. The increased formation of the protein interferon-gamma, which has immune-stimulating properties, is important for the changed function of the Tregs.

The messenger substance IL-33 could therefore possibly offer a starting point at which the Tregs in the tumor can be targeted and modified in their functionality. On the other hand, a less targeted attack on all Tregs present in the body can lead to life-threatening autoimmune reactions. IL-33 is thus a potential target that future therapies could focus on in order to advance the immune system's fight against cancer.

publication
Aikaterini Hatzioannou, Aggelos Banos, Theodore Sakelaropoulos, Constantinos Fedonidis, Maria-Sophia Vidali, Maren Koehne, Kristian Händler, Louis Boon, Ana Henriques, Vasiliki Koliaraki, Panagiotis Georgiadis, Jerome Zoidakis, Aikafaterini Termentzi, Marc Beyer, Travianiantini Aristotelis Tsirigos and Panayotis Verginis: An intrinsic role of IL-33 in Treg cell – mediated tumor immunoevasion
Nature Immunology DOI: 10.1038 / s41590-019-0555-2

Contact for the press:
Dr. Anna Kraft
National Center for Tumor Diseases Dresden (NCT / UCC)
Press and public relations
Tel .: +49 (0) 351 458-5548
Email: [email protected]
www.nct-dresden.de

Dr. Sibylle Kohlstädt
German Cancer Research Center (DKFZ)
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Stephan Wiegand
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Medical Faculty Carl Gustav Carus of the Technical University of Dresden
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01307 Dresden
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Email: [email protected]
www.tu-dresden.de/med

Holger Ostermeyer
Carl Gustav Carus University Hospital Dresden press office
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01307 Dresden
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Email: [email protected]

www.uniklinikum-dresden.de

Dr. Christine Bohnet
Communication and media | Head
Helmholtz Center Dresden-Rossendorf
Bautzner Landstrasse 400 | 01328 Dresden
Email: [email protected]
Tel .: +49 351 260-2450 | +49 160 969 288 56 | Fax: +49 351 260-2700
www.hzdr.de

NCT / UCC Dresden
Since 2015, Dresden has been the second location of the National Center for Tumor Diseases (NCT) alongside Heidelberg. The Dresden Center is a joint facility of the German Cancer Research Center (DKFZ), the Carl Gustav Carus University Hospital Dresden, the Medical Faculty of the Technical University of Dresden and the Helmholtz Center Dresden-Rossendorf (HZDR).
The NCT has set itself the task of linking research and health care as closely as possible. This means that cancer patients in Dresden and Heidelberg can be treated according to the latest scientific findings. At the same time, the proximity of the laboratory and clinic gives the scientists important impulses for their practical research. The common aim of both locations is to develop the NCT into an international top center for patient-centered cancer research. The Dresden Center builds on the structures of the University Cancer Center Dresden (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. Since 2007, the UCC has been continuously recognized by the German Cancer Aid e.V. (DKH) as an "Oncological Top Center".

German Cancer Research Center (DKFZ)
The German Cancer Research Center (DKFZ) is the largest biomedical research institution in Germany with more than 3,000 employees. Over 1000 scientists at the DKFZ are researching how cancer develops, recording cancer risk factors and looking for new strategies to prevent people from developing cancer. They are developing new methods with which tumors can be diagnosed more precisely and cancer patients treated more successfully. The employees of the Cancer Information Service (KID) educate those affected, relatives and interested citizens about the widespread disease cancer. Together with the Heidelberg University Hospital, the DKFZ has set up the National Center for Tumor Diseases (NCT) Heidelberg, in which promising approaches from cancer research are transferred to the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translation centers at seven university partner locations. The combination of excellent university medicine with the top-class research of a Helmholtz center is an important contribution to improving the chances of cancer patients. The DKFZ is financed 90 percent by the Federal Ministry of Education and Research and 10 percent by the State of Baden-Württemberg and is a member of the Helmholtz Association of German Research Centers.

Carl Gustav Carus University Hospital Dresden
The Carl Gustav Carus University Hospital Dresden offers medical care at the highest level of care. As a maximum care hospital, it covers the entire spectrum of modern medicine. The university hospital brings together 20 clinics and polyclinics, four institutes and ten interdisciplinary centers that work closely with the clinical and theoretical institutes of the medical faculty.
With 1,295 beds and 160 places for day-care treatment of patients, the Dresden University Hospital is the largest hospital in the city and at the same time the only maximum care hospital in East Saxony. Around 860 doctors cover the entire spectrum of modern medicine. 1,860 nurses take care of the patients. Important treatment priorities of the university hospital are the care of patients suffering from cancer, metabolic and neurodegenerative diseases.
Germany's largest hospital comparison by the news magazine “Focus” attests that the Carl Gustav Dresden University Hospital has an excellent quality of treatment. The Dresden University Medicine is therefore in second place in the Germany-wide ranking.

Medical Faculty Carl Gustav Carus of the Technical University of Dresden
The University Medicine Dresden, consisting of the Medical Faculty Carl Gustav Carus and the University Hospital of the same name, has specialized in research in the areas of oncology, metabolic, neurological and psychiatric diseases. In these focal points, the topics of degeneration and regeneration, imaging and technology development, immunology and inflammation as well as prevention and health services research are of particular interest. International exchange is a prerequisite for cutting-edge research - the University Medicine Dresden lives this idea with employees from 73 nations as well as numerous collaborations with researchers and teams all over the world.

Helmholtz Center Dresden-Rossendorf (HZDR)
The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) conducts research in the fields of energy, health and matter. The focus here is on the following questions:
• How do you use energy and resources efficiently, safely and sustainably?
• How can cancer diseases be better visualized, characterized and effectively treated?
• How do matter and materials behave under the influence of high fields and in the smallest of dimensions?
To answer these scientific questions, the HZDR operates large infrastructures that are also used by external measurement guests: the ion beam center, the Dresden high-field magnet laboratory and the ELBE center for high-power radiation sources.
The HZDR is a member of the Helmholtz Association, has five locations (Dresden, Freiberg, Grenoble, Leipzig, Schenefeld near Hamburg) and employs almost 1,200 people - including around 500 scientists including 170 doctoral students.

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