Scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and Dresden University Medicine, together with an international team of researchers, were able to demonstrate that certain white blood cells, so-called neutrophil granulocytes, can potentially - after completing a special training programme - be utilised for the treatment of tumours. In order to stimulate the training of this part of the innate immune system, the scientists used beta-glucan, a long-chain sugar molecule that occurs as a natural fibre mainly in the cell walls of fungi, oats or barley. The immune training already became effective at the level of blood formation in the bone marrow, in the precursor cells of the neutrophil granulocytes. Based on this newly described mechanism, it is possible that novel cancer immunotherapies which improve treatment for cancer patients will be developed in the future. The scientists published their results in the renowned specialist journal Cell.
The National Center for Tumor Diseases Dresden (NCT/UCC) is a joint institution of the German Cancer Research Center (DKFZ), the University Hospital Carl Gustav Carus Dresden, Carl Gustav Carus Faculty of Medicine at TU Dresden and the Helmholtz- Zentrum Dresden-Rossendorf (HZDR).
Tumour cells can evade the immune system in a variety of ways and in this manner nullify its protective effect. Immunotherapies aim at preventing these evasive manoeuvers and at redirecting the natural defence mechanisms in the patient's body against the cancer cells.
Modern immunotherapies rely on the specialists of our defence system, such as T cells, dendritic cells or certain antibodies. As part of the specific immune system, these are able to recognise suitable structures on tumour or immune cells and initiate or execute a precisely tailored defence reaction. For the first time, scientists at the National Center for Tumor Diseases Dresden (NCT/UCC) and University Medicine Dresden were now able to demonstrate that even the non-specific immune response of our body can - through special training - be weaponised against tumours. "Based on the mechanism described, new forms of cancer immunotherapy are conceivable which could improve the chances for treatment for certain patients in the future," says Prof. Triantafyllos Chavakis, Director of the Institute of Clinical Chemistry and Laboratory Medicine (IKL) of the University Hospital Carl Gustav Carus Dresden.
Training of neutrophil granulocytes inhibits tumour growth
At the centre of the described mechanism are special immune cells, so-called neutrophil granulocytes - or neutrophils for short. These form the most common subgroup of the white blood cells and are part of the innate, non-specific immune defence. In contrast to the specific part of our immune system - which first analyses foreign structures in the body in detail and then, with a time lag, activates tailor-made defence mechanisms - the non-specific part of the body's own defence acts as a rapid response force: if pathogens enter the body or cells degenerate, it reacts very quickly and mostly stereotypically.
However, certain stimuli can also influence - or even train - the non-specific immune response. Training causes certain actors of the rapid response force to exhibit altered properties and perform their tasks better and over a longer period of time than before: the impact of the rapid response force increases. The researchers have now been able to demonstrate for the first time that this effect, which is already known to occur in infections, can also be used against tumours.
The neutrophil granulocytes play an important role in this process. In certain tumours, they accumulate in the environment of the tumour or migrate into it. These "tumour-associated neutrophils" - located directly at the tumour - can inhibit tumour growth, but some also have tumour-promoting properties. It is assumed that the tumour itself releases substances that turn the neutrophils into drivers of tumour growth. In experimental models, the scientists were able to partially reverse this process, which is detrimental to healing, by specially training the non-specific immune response. In order to stimulate the immune system, they used the long- chain sugar molecule (polysaccharide) beta-glucan. This is a natural fibre found mainly in the cell walls of fungi, oats or barley. Administrating beta-glucan caused the proportion of neutrophils with tumour-inhibiting properties to increase significantly and tumour growth to decrease.
Change in blood formation ensures long-term effect
Of particular importance in this context was proving that the reprogramming of neutrophil granulocytes already begins in the bone marrow. Here, from stem cells, various precursor cells develop and it is from these that the different blood cells emerge. The administration of beta-glucan altered the gene activity of the myeloid precursor cells. The neutrophils later also develop from these. "This causes the properties of the short-lived neutrophils to change in the longer term, towards activity directed against the tumour. This is because the precursor cells form neutrophils with tumour-inhibiting properties over a longer period of time," explains joint first author Lydia Kalafati from IKL and NCT/UCC.
As the next step, it would be conceivable to utilise the principle of neutrophil training in combination with already approved immunotherapies in cancer patients. "In doing so, we also want to investigate in which types of tumours the method works particularly well, in order to then use it in a very targeted manner in future," says Prof. Martin Bornhäuser, member of the Managing Directorate of the NCT/UCC and Director of the Department of Medicine I of the University Hospital Dresden.
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Since 2015, Dresden has been the second site of the National Center for Tumor Diseases (NCT), alongside Heidelberg. The Dresden Center is a joint institution of the German Cancer Research Center (DKFZ), the University Hospital Carl Gustav Carus Dresden, Carl Gustav Carus Faculty of Medicine at TU Dresden and the Helmholtz-Zentrum Dresden-Rossendorf (HZDR). The NCT has made it its mission to link research and patient care as closely as possible. That is why cancer patients in Dresden and Heidelberg can be treated based on the latest scientific findings. At the same time, the close proximity of laboratory and clinic provides scientists with important impulses for their practice-oriented research. Joint aspiration of both sites is to establish the NCT as an internationally renowned centre of excellence in personalised cancer research. The Dresden Center builds on the structures of the University Cancer Center (UCC), which was founded in 2003 as one of the first Comprehensive Cancer Centers (CCC) in Germany. From 2007 onwards, German Cancer Aid (DKH) has continuously honoured the UCC as Oncology Center of Excellence.
German Cancer Research Center (DKFZ)
With its more than 3,000 employees, the DKFZ is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, document cancer risk factors and search for new strategies to prevent people from developing cancer. The scientists are developing new methods to diagnose tumours more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on the subject of cancer. Together with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) at the sites in Heidelberg and Dresden, and also the Hopp Children's Tumour Center "KiTZ" in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centres for Health Research, the DKFZ maintains translational centres at seven university partner locations. The combination of excellent university medicine with the high-quality research of a Helmholtz Centre at the NCT and DKTK sites is an important contribution to transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients. 90 percent of the DKFZ's funding comes from the Federal Ministry of Education and Research, and 10 percent from the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centres. .
University Hospital Carl Gustav Carus Dresden
The University Hospital Carl Gustav Carus Dresden offers medical care at the highest level. As a hospital of maximum care, it covers the whole range of modern medicine. The University Hospital combines 20 clinics and policlinics, four institutes and ten interdisciplinary centres that work closely together with the clinical and theoretical institutes of the Faculty of Medicine. With 1,295 beds and 160 units for out-patient treatment, the Dresden University Clinic is the largest hospital in the city and also the only hospital of maximum care in East Saxony. About 860 doctors cover the whole range of modern medicine. 1,860 female and male nurses take care of the well-being of our patients. The focus of treatment is on patients suffering from cancer and from metabolic and neurodegenerative diseases.
Germany's largest comparison of hospitals carried out by Focus news magazine confirms the excellent quality of care at University Hospital Carl Gustav Carus Dresden. Dresden University Medicine is therefore ranked second nationwide.
Carl Gustav Carus Faculty of Medicine at TU Dresden
Dresden University Medicine, consisting of the Carl Gustav Carus Faculty of Medicine and the University Hospital of the same name, focuses its research on oncology, and on metabolic as well as neurological and psychiatric diseases. Of particular interest for these focal points are the subject areas of degeneration and regeneration, imaging and technology development, immunology and inflammation as well as prevention and health care research. International exchange is a prerequisite for cutting- edge research. Dresden University Medicine embodies this idea with employees from 73 nations as well as numerous collaborations with researchers and teams from around the world.
Helmholtz-Zentrum Dresden-Rossendorf (HZDR)
The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) conducts research in the areas of energy, health and materials, with the focus on the following challenges:
- How can energy and resources be utilised in an efficient, safe and sustainable way?
- How can cancerous diseases be more precisely visualised, characterised and treated effectively?
- How do matter and materials behave under the influence of strong fields and in the smallest dimensions?
In order to answer these scientific questions, the HZDR maintains large infrastructures that are also available to external users: Ion Beam Center, Dresden High Magnetic Field Laboratory and ELBE Center for High-Power Radiation Sources. The HZDR is a member of the Helmholtz Association, operates six sites (Dresden, Freiberg, Görlitz, Grenoble, Leipzig, Schenefeld near Hamburg) and employs nearly 1,200 members of staff, including 500 scientists, 170 of whom are doctoral candidates.