How Specialized Immune Cells Can Detect "Invisible" Tumors

Scientists from the Netherlands Cancer Institute and Leiden University Medical Center (LUMC) have discovered the way in which specialized immune cells can detect and remove cancers that are "invisible" to the conventional defense mechanisms employed by the immune system. The findings could lead to new immunotherapies against cancer.

The findings of Emile Voest, Joris van de Haar, Myriam Chalabi, Vivien Veninga and others have now been published in Nature.

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

Molecules for recognition

Cancer cells are only recognized by T cells if a specific molecule is attached to their surface. To circumvent this immune recognition, some cancer cells lack such molecules, making them "invisible" to T cells.

Recently, researchers from LUMC and NKI stumbled upon a strange phenomenon: some patients with "invisible" cancers respond very well to immunotherapy. These kinds of therapies rely on antibodies that activate or reinvigorate the activity of T cells. “Since these cancer types don't display the molecules that enable T cells to identify them, we did not understand why these patients were responding so well to the therapy,” says Noel de Miranda, associate professor at LUMC Department of Pathology.

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

Backup system

De Miranda: “This shows that our immune systems have a backup in place. If the main mechanism of recognizing tumor cells doesn't work, we come equipped with a second line of defense. Our findings could eventually lead to new treatments with γδ T cells for ‘invisible’ tumors.

“We have only just begun to uncover the tremendous potential that γδ T cells carry for the development of new immunotherapies against cancer”, says Emile Voest, professor of Medical Oncology and group leader at the Netherlands Cancer Institute. “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 new immunotherapies. They will be particularly important to treat tumors that ‘conventional’ T cells don't destroy.”

Reference: de Vries NL, van de Haar J, Veninga V, et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects. Nature. Published online January 11, 2023. doi: 10.1038/s41586-022-05593-1

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