T cells more effective against tumor cells when they work together

So-called cytotoxic T cells are effective ‘soldiers of the immune system’ capable of killing a single blood cancer cell up to 20 times a day. However, in larger tumor cells, a single T cell is much less effective. An attack then only rarely leads to the death of a tumor cell.

Collaborating T cells more effective

When T cells to collaborate, as scientists at Radboudumc have shown, they do succeed in killing larger tumor cells more effectively. The scientists let in a publication in Nature Communications see exactly how the collaborating T cells work, how they irreparably damage the tumor cells and how tumor cells try to repair the damage caused.

For the research, the scientists used skin cancer cells. They examined the contact between the T cells and skin cancer cells under a special microscope for living cells. To simulate these interactions, the researchers developed 3D computer models. With this research they were able to demonstrate, and literally saw, that tumor cells that were attacked at least three times by a T-cell within three hours eventually died.

In four out of five cases, the tumor cells were attacked by multiple T cells. The lower the concentration of T cells, the smaller the damage that was done and thus the chance of recovery of the tumor cell increased. The conclusion is therefore: The more T cells besiege the tumor cell, the better.

Improving cancer therapy

“We already knew that T cells and tumor cells make regular contact with each other. But what exactly happens between the cells? We see that during half of the interactions the T cell causes damage to the tumor cell, by causing holes in the cell membrane, tears in the nuclear membrane and damage to the DNA. This should not be seen as shooting with a bazooka, but more like cutting with a small knife. If a T cell only cuts once, the tumor cell can still repair the damage, just like we can recover from a cut. But more damage in a short time can kill the tumor cell,” says Peter Friedl, professor of Microscopic Cell Imaging at Radboudumc.

The scientists’ research and findings provide new leads for improving cancer therapy. Professor Friedl about this: “We show that multiple blows that individually do not lead to the death of the tumor cell, can do so together. You want to encourage that further. For example, with drugs that ensure a longer binding of the T cell to the tumor cell via so-called activating check points. These drugs bind to the T-cell and stimulate the immune response against tumor cells. We have already shown that a single T cell then causes multiple damage to the same tumor cell. You can also give very low doses of chemotherapy or radiation, so that damage adds to the damage caused by the T cells. We expect that this will make the tumor cell more sensitive and that it will die faster.”

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