Finding could lead to development of a new breast cancer treatment that prevents key protein on tumour cells from binding to immune cells
Scientists funded by Breast Cancer Now have identified a mechanism by which breast cancers are able to bind to white blood cells in the cancer's local environment, helping to protect the tumour from the body's immune system and promote its growth.
As well as containing tumour cells, breast cancers contain many different types of healthy cells, including cells from the immune system. These immune cells have the potential to help destroy the cancer, but tumour cells have found ways to stop immune cells from carrying out their normal functions, enabling a cancer to continue to grow and progress.
The study - published today in the journal Nature Immunology - demonstrates that a glycoprotein specific to tumour cells, called MUC1-ST, is able to bind to a receptor on nearby white blood cells, enabling breast cancers to commandeer these immune cells. In doing so, these immune cells are 'educated' by the tumour to begin producing molecules that help to promote its growth and protect the cancer from attack by the body's natural defences.
The scientists - led by Professor Joy Burchell and Dr Richard Beatson at King's College London - examined this process by isolating immune cells from the blood of over 40 healthy donors from the National Blood Transfusion Service, and growing them with the MUC1-ST protein in the lab to study their reactions. Their investigations found that when attached to MUC1-ST, the immune cells released a number of molecules known to help tumour growth and movement.
The researchers also sought to understand how MUC1-ST was able to attach itself to the immune cell receptor. Many proteins found on the cell surface have sugars attached to them - but the types of sugars attached to proteins on breast cancer cells are different to those seen on the same protein on normal cells.
When the researchers grew immune cells with the MUC1 protein 'decorated' with a different form of sugar, they did not see any interaction or changes to white blood cells, suggesting that it is the sugars found on the MUC1-ST protein in breast cancer cells that enables it to bind to the immune cell receptors.
The finding could lead to the development of a new treatment for breast cancer patients that works by preventing the MUC1-ST protein on the surface of cancer cells from binding to cells in the immune system. The next step for developing this kind of treatment would be testing in mice - if that work was successful, it could then progress to clinical trials in humans, which the authors believe could be possible in the next five years.
This new type of treatment could be combined with existing immunotherapy drugs - that have already proved effective in treating melanoma (skin cancer) and lung cancer - to create a 'two-pronged' approach to helping the immune system to fight back against breast cancers.
Study leader Joy Burchell, Professor of Glyco-Oncology at King's College London, said:
"This research shows a completely new way in which breast cancer cells modulate the local environment to allow them to grow and evade the immune response.
"In the short term, this finding will form the basis for more research to develop new treatments that stop the cancer cells from modulating the immune system. We have already shown that we are able to block these effects with some agents and this now needs to be tested in preclinical models."
Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, said:
"This study represents a step forward in our understanding of how breast cancers can manipulate healthy cells to allow them to escape the body's natural immune response.
"While these exciting early lab results must now be confirmed in further studies, they could give us an important insight into how we might stop breast cancers from avoiding the immune system.
"This would be an entirely new approach to treating breast cancer and could be particularly important for cancers that do not respond to existing treatments."
The study was majority-funded by Breast Cancer Now with additional funding from the Medical Research Council (MRC).Article: The mucin MUC1 modulates the tumor immunological microenvironment through engagement of the lectin Siglec-9, Richard Beatson, Virginia Tajadura-Ortega, Daniela Achkova, Gianfranco Picco, Theodora-Dorita Tsourouktsoglou, Sandra Klausing, Matthew Hillier, John Maher, Thomas Noll, Paul R Crocker, Joyce Taylor-Papadimitriou, Joy M Burchell, Nature Immunology, doi:10.1038/ni.3552, published online 5 September 2016.