Immune cells called Gamma Delta T cells can act independently to identify and kill cancer cells, defying the conventional view of the immune system, reveals new research from the Francis Crick Institute and King's College London.

The study, published in Nature Immunology, reveals that Gamma Delta T cells possess a unique two-pronged device, allowing them to double-check whether the body's cells are healthy or dangerous before deciding whether to kill them. Moreover, they can do this without relying on 'authorization' from other immune signals.

"These maverick immune cells act as judge, jury, and executioner, identifying and killing potentially dangerous cells in the body," said Professor Adrian Hayday, whose teams at the Crick and King's led the latest study.

The immune system

"This discovery was a huge surprise. It fundamentally changes our understanding of how the immune system makes critical judgment calls about when to act and when to hold back. This could open up exciting possibilities for treating disease," said Hayday.

Adrian is working with GammaDelta Therapeutics, a spin-out company that he co-founded, together with the Crick, King's and Cancer Research UK, to apply the findings clinically. The company has a $100 million collaboration with pharmaceutical giant Takeda to develop new treatments using these single cells, with the aim of starting human trials within two years.

"We are not only looking at how to harness Gamma Delta cells to tackle cancers, but we are also investigating their role in autoimmune conditions such as inflammatory bowel disease," said Adrian. "The prospect of turning them to be less forgiving of tumor cells or more forgiving of healthy cells is genuinely fascinating."

For the past two decades, it has been dogma that the immune system is made up of two distinct subsystems: the 'innate' immune system, which offers us broad protection by detecting when things simply are not normal; and the specialised 'adaptive' immune system which can discriminate and respond to very specific threats.

The new study challenges this view, providing the first direct evidence that a single protein on a single cell type can perform both functions, detecting when things aren't healthy and then mounting a specific response.

Equipped with these unprecedented capabilities, Gamma Delta T cells patrol for pathogens or dangerously mutated cells arising in expansive body tissues, such as the skin and the gut. The new research found that the cells use two different checks to make sure they don't kill a healthy cell: checking if the cell looks dangerous but also whether it is nonetheless functioning normally.

For example, if the Gamma Delta T cells see a gut cell that appears slightly mutated, but that is still normal by many other criteria, they will likely leave it alone. Without this type of check, the immune system could unleash uncontrolled attacks on healthy tissue.