idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
idw - Informationsdienst
Wissenschaft
MHH researchers discover sugar structures on kidney cells that can predict response to treatment with immune checkpoint inhibitors.
Among modern cancer therapies, immune checkpoint inhibitors (ICI) are among the most successful treatment methods. These antibodies activate the immune system and enable T cells to detect and destroy tumour cells. Immune checkpoint inhibition is also an important part of the treatment for clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer. It is used when metastases have already formed and surgery alone cannot control the cancer. However, the treatment is not only expensive but also has side effects. In addition, not all patients respond to immunotherapy. Currently, however, there is no way to predict which patients with ccRCC will actually benefit from ICI.
A research team led by Professor Jan Hinrich Bräsen, Executive Director of the Institute of Pathology and Medical Director of the Working Group Nephropathology at Hannover Medical School (MHH), has now identified biomarkers that could answer this question. While many researchers focus on genes or proteins in their search for such biological fingerprints, the nephropathologist has turned his attention to a completely different group of substances: sugars. In a study, the research team discovered two sugar structures that can be used to predict on an individual basis who will respond to ICI treatment and who will not. These biomarkers could serve as a guide for individualised treatments and minimise unnecessary ICI therapies.
ICI removes the camouflage of tumour cells
Our body's own defence system is active around the clock to fight pathogens and eliminate degenerated cells before they can develop into a malignant tumour. But cancer cells have various tricks up their sleeves to hide from the immune system. One of these involves the immune system's T cells, which are supposed to detect tumour cells. They do this with the help of specific receptors on their surface, known as immune checkpoints. These function according to the lock-and-key principle, enabling the T cells to distinguish between the body's own healthy cells and diseased and degenerate ones. As control points, the immune checkpoints then slow down or activate the immune defence accordingly. Cancer cells exploit this protective mechanism by binding to the checkpoints like healthy body cells and disguising themselves as harmless cells, so to speak. This allows them to evade the immune system. Immune checkpoint inhibitors block the binding of checkpoint proteins to their partner proteins on cancer cells. This prevents the shutdown signal and makes cancer cells visible to T cells again.
Diversity of sugar structures greater than genetic diversity
Why this mechanism does not work equally well in every person with ccRCC remains a mystery. The research team suspected that sugar structures might play a role. ‘In our bodies, every cell has a jungle of sugar structures, so to speak, which must have some function,’ notes Professor Bräsen. These look different in every person and are more diverse than our genetic differences. The sugar compounds, known as glycans in technical terminology, exist on all body cells, including kidney cells. To analyse the sugar compounds, the researchers collaborated with a working group at the Medical University of South Carolina (MUSC) and used MALDI imaging mass spectrometry. This is an imaging method for analysing chemical compounds and their spatial distribution in a sample. In addition, tissue sections stained for immune markers and immune cells were scanned, digitised and evaluated with the aid of AI in an almost completely automated process using a motorised high-performance microscope. ‘This enabled us to assign these kidney glycans to their respective kidney regions, such as nephrons and tubules, and create a general atlas of sugar distribution in healthy kidneys,’ says Jessica Schmitz, Scientific Director of the Working Group Nephropathology. The researchers then compared the cell surfaces in healthy kidneys and ccRCC tumours and analysed their sugar structures in collaboration with sugar experts at MUSC.
Sugar biomarkers identify ICI responders
After removal of the tumour, the patients were treated with ICI. It was noticed that two specific types of sugar were found in increased amounts in the group of non-responders, i.e. patients who did not respond to immunotherapy. ‘These N-glycans are promising biomarker candidates for identifying responders and non-responders even before ICI treatment,’ says Professor Bräsen. After all, according to Dr Philipp Ivanyi, senior physician at the Department for Haematology, Haemostasiology, Oncology and Stem Cell Transplantation at MHH, where the patients were treated, up to a third of people with ccRCC tumours are non-responders. They could be spared complex and expensive immunotherapy – and possible serious side effects that occur when the activated immune system attacks healthy organs. However, before the sugar biomarkers can be incorporated into everyday clinical practice, they must be investigated further.
SERVICE:
Further information is available from Professor Dr Jan Hinrich Bräsen, Braesen.Jan@mh-hannover.de.
The original paper, ‘Spatial atlasing of N-glycosylation in healthy control and clear cell renal cell carcinoma tissues linked with immune checkpoint inhibition response by MALDI mass spectrometry imaging,’ can be found here: https://www.sciencedirect.com/science/article/pii/S0003267025011183
Professor Dr Jan Hinrich Bräsen and Jessica Schmitz examined sugar structures on kidney tissue using ...
Copyright: Karin Kaiser/MHH.
Criteria of this press release:
Journalists
Medicine
transregional, national
Research results, Scientific Publications
English
You can combine search terms with and, or and/or not, e.g. Philo not logy.
You can use brackets to separate combinations from each other, e.g. (Philo not logy) or (Psycho and logy).
Coherent groups of words will be located as complete phrases if you put them into quotation marks, e.g. “Federal Republic of Germany”.
You can also use the advanced search without entering search terms. It will then follow the criteria you have selected (e.g. country or subject area).
If you have not selected any criteria in a given category, the entire category will be searched (e.g. all subject areas or all countries).
