Researchers at the University of Cambridge hope to revolutionise cancer therapy after discovering one of the reasons why many previous attempts to harness the immune system to treat cancerous tumours have failed.
New research, published today in the journal Science, reveals that a type of stromal cell found in many cancers which expresses fibroblast activation protein alpha (FAP), plays a major role in suppressing the immune response in cancerous tumours – thereby restricting the use of vaccines and other therapies which rely on the body's immune system to work. They have also found that if they destroy these cells in a tumour immune suppression is relieved, allowing the immune system to control the previously uncontrolled tumour.
Douglas Fearon, Sheila Joan Smith Professor of Immunology of the Department of Medicine at the University of Cambridge, said: "Finding the specific cells within the complex mixture of the cancer stroma that prevents immune killing is an important step. Further studying how these cells exert their effects may contribute to improved immunological therapies by allowing us to remove a barrier that the cancer has constructed."
Vaccines created to prompt the immune system to attack cancerous cells in tumours have shown to activate an immune response in the body but have, inexplicably, almost never affected the growth of tumours. Immunologists who specialise in tumours have suspected that within the tumour microenvironment the activity of immune cells is somehow suppressed, but they have thus far been unable to fully reverse this suppression.
The new research, funded by the Wellcome Trust and the Sheila Joan Smith Professorship endowment, sheds light on why the immune response is suppressed. The Cambridge study found that at least one immune suppressive component is contained within normal tissue cells (called stromal cells) the cancer has coerced to assist its survival. The cell they studied specifically expresses a unique protein often associated with wound healing - fibroblast activation protein alpha (FAP). The FAP expressing cells are found in many cancers, including breast and colorectal cancers.
In order to determine if FAP expressing stromal cells contribute to the resistance of a tumour to vaccination, the researchers created a transgenic mouse model which allowed them to destroy cells which expressed FAP. When FAP-expressing cells were destroyed in tumours in mice with established Lewis lung carcinomas (of which only 2% of the tumour cells are FAP-expressing), the cancer began to rapidly 'die'. The Fearon lab now hopes to collaborate with scientists at the CRUK Cambridge Research Institute to evaluate the effects of depleting FAP-expressing cells in a mouse model that more closely resemble human cancer, and to examine FAP-expressing cells of human tumours.
Professor Fearon continued: "These studies are in the mouse, and although there is much overlap between the mouse and human immune systems, we will not know the relevance of these findings in humans until we are able to interrupt the function of the tumour stromal cells expressing FAP in patients with cancer.
"It should be noted, however, that the FAP-expressing stromal cell was actually first found in human cancer by Lloyd Old and his colleagues 20 years ago."For additional information please contact:
2. The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust's breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
Genevieve Maul | EurekAlert!
Show me your leaves - Health check for urban trees
12.12.2017 | Gesellschaft für Ökologie e.V.
Liver Cancer: Lipid Synthesis Promotes Tumor Formation
12.12.2017 | Universität Basel
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
12.12.2017 | Physics and Astronomy
12.12.2017 | Earth Sciences
12.12.2017 | Power and Electrical Engineering