Oncode Investigators Emile Voest, Ton Schumacher and Lodewyk Wessels (all NKI), together with scientists from Leiden University Medical Center (LUMC) have discovered how specialized immune cells can detect and remove cancers that are ‘invisible’ to the conventional defense mechanisms of the immune system. The findings could lead to novel cancer immunotherapies. Their work is published today in Nature.

“By linking clinical data with preclinical research and bioinformatics, in line with the mission and vision of Oncode, we have identified new insights on how immune cells kill tumors” says Oncode Investigator Emile Voest, Professor of Medical Oncology and group leader at the Netherlands Cancer Institute.

Normally, the recognition of abnormal cells in our body is a task for T cells, one of the most important white blood cells of the immune system. These cells can recognize many types of abnormalities, including viral and bacterial infections. But the immune system sometimes has trouble detecting cancer cells.

Cancer cells are only recognized by T cells if a specific molecule is attached to their surface. In order to escape immune recognition, some cancers lack such molecule and become ‘invisible’ to T cells.

In their collaborative work, the researchers stumbled upon a strange phenomenon: some patients with ‘invisible’ cancers respond very well to cancer immunotherapies. These therapies rely on antibodies that activate or reinvigorate the activity of T cells. “Since these cancers lack the molecules which enable T cells to identify them, we did not understand why patients responded so well to the therapy,” says Noel de Miranda, Associate Professor at LUMC Department of Pathology.

Research on cells drawn from patients that were treated at NKI now shows that gd T cells - a lesser known, specialized immune type of cell - are capable of detecting cancers that are invisible to conventional T cells.

“This shows that there is a backup system in our immune system. When the main way of recognizing tumor cells does not work, we have a second line of defense. Our findings could eventually lead to new treatments for ‘invisible’ tumors with gd T cells” says de Miranda.

“We are only beginning to unveil the tremendous potential that gd T cells carry for the development of novel cancer immunotherapies”, says Voest.

“Going forward, we will try to gain a better understanding of how these immune cells work in the body of cancer patients, and how we can make use of them to develop novel immunotherapies. They will be particularly important to treat cancers that are not susceptible to elimination by ‘conventional’ T cells” he adds.

This research has been financially supported by Oncode Institute and The European Research Council.