New research helps explain how tumours go undetected by the body
19 November 2007
Scientists studying how immune cells are regulated in healthy individuals, have made a key discovery in understanding why tumours may go undetected by the immune system and remain untreated by the body’s own natural defences. The findings, published online this week (between 19 - 23 November) by the Proceedings of the National Academy of Sciences, could lead to new treatments for tumours.
Under normal circumstances, the immune system creates sustained inflammation around a dangerous pathogen or injury which tells the body that there is a problem. However, in the case of tumours, certain cellular mechanisms counteract inflammation which can cause the tumour to go undetected, making it even harder for the body to expel.
The researchers at King’s College London, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), discovered that regulatory T cells can reverse the role of a key immune cell called a macrophage which is normally involved in causing inflammation. Regulatory T cells are cells that regulate the immune system to stop it over-responding to every external stimulus and only deal with genuinely harmful pathogens or injuries. The research shows that they can achieve this by encouraging macrophages to instead dampen down the inflammatory response that is automatically induced by all possible threats to the body, even those that turn out to be harmless.
Dr Leonie Taams, research leader explains: “A relatively harmless stimulus, such as a small cut, will automatically be treated by the body as something dangerous and will cause macrophages to promote inflammation. We discovered that it is then the regulatory T cells’ responsibility to make the macrophages promote anti-inflammation to counteract the initial response, as it is not a real danger. This helps keeps the immune system stable and prevents the body over-reacting to everything in its environment.
“However problems can occur with tumours, where many regulatory T cells promoting a strong anti-inflammatory response are present. Neutralising an inflammatory response in this scenario can cause the tumour to fall under the radar of the body's immune system and ‘trick’ it into believing that there is no problem.
“We hope to be able to use this new knowledge about the relationship between regulatory T cells and macrophages to find more effective treatments for tumours. Interestingly, we also hope to use the same knowledge to achieve the opposite result and block chronic inflammation such as that which occurs in rheumatoid arthritis.”
Notes to editors
This research is detailed in the article 'CD4+CD25+ regulatory T cells induce alternative activation of human monocytes/macrophages', authored by Machteld M. Tiemessen, Ann L. Jagger, Hayley G. Evans, Martijn J. C. van Herwijnen, Susan John and Leonie S. Taams. The article will be published in an online Early Edition (EE) of the Proceedings of the National Academy of Sciences (PNAS), between 19-23 November 2007 at http://www.pnas.org/papbyrecent.shtml.
Note that these images are protected by copyright law and may be used with acknowledgement of Dr Leonie Taams, King’s College London.
Click on the images for a larger version.
Macrophages treated with regulatory T cells. In contrast to macrophages treated with non-regulatory T cells, there are fewer inflammatory cells, indicated by fewer red cells. There are also more anti-inflammatory cells, indicated by the greater number of green cells.
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £380 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. http://www.bbsrc.ac.uk
The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public's needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. http://www.mrc.ac.uk
Dr Leonie Taams, King’s College London
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