Competition between immune cells could explain why some immunotherapy drugs fail

New images may have uncovered why in some cases cancers don’t respond to certain immunotherapy drugs.

Research published in the journal Science Translational Medicine found that, in mice, one type of immune cell competes with another by binding to the drug.

The treatments – called checkpoint inhibitors – are targeted to the immune system’s T cells. But the research found that a different immune cell, called a macrophage, can snatch the drugs away, making them ineffective.

Professor Tim Elliott, from Cancer Research UK’s Southampton centre, said that the research suggests a new way in which these drugs could be made to work better and in more patients.

Cancer can escape detection by the immune system by using an ‘off-switch’ on immune cells.

Checkpoint inhibitors block a molecule on the immune system’s T-cells called PD-1, stopping the cancer cell’s ability to use this switch. This frees up the immune system to recognise and destroy the cancer.

Such treatments have improved survival for some patients, particularly those with advanced melanoma and lung cancer. But they don’t work in all cases.

The latest research from Massachusetts General Hospital in the US used specialised microscopes to track living cells in mice. The researchers found that the checkpoint inhibitors can be removed from their target T-cells by another kind of immune cell, called a macrophage, which could happen within 20 minutes of treatment.

Elliott said that the work adds to the evidence that certain molecules on the surface of macrophages can make or break the effectiveness of treatment.

Despite the clear success that immunotherapies are showing in the clinic, we still know relatively little about how they work,” he said. “And we don’t know why some patients benefit while others don’t.

“This study shows that to improve the next generation of immunotherapy treatments we need to know more about how these drugs interact with other immune cells that are found in tumours, like macrophages.” 

• Watch: What are ‘checkpoint’ immunotherapy drugs?

Dr Mikael Pittet, senior author of the research, said that by discovering what was happening, they were able to devise ways to extend the time the drug sticks to the target T cells, and improve the effectiveness of the treatment in mice.

The researchers located the part of macrophages responsible for snatching away the checkpoint inhibitor, and were able to block the interaction.

Once competition from the macrophages was halted, the checkpoint inhibitor was able to stick properly to T cells, freeing them to attack and shrink tumours in mice.

The researchers said that whether a similar strategy could improve the results of immunotherapy in humans may be answered by clinical trials that combine immune checkpoint blockers with drugs targeting macrophages