First immune 'danger receptor' found

16 February 2009

London Research Institute (LRI) scientists have found the first biological receptor that alerts the immune system to 'dangerous' or abnormal cell death, according to research published in Nature * today (Sunday).

Cell death is a normal process and essential for keeping tissue healthy. But sometimes cells undergo an abnormal form of death - called necrosis - in response to a trauma or injury.

It has long been suspected that sensing this type of cell death could kick-start an immune response because an injury could be accompanied by an infection. But, until now, a receptor with this function had not been found.

The discovery of a 'danger receptor' could improve our understanding of how immune cells work and help cancer drug discovery.

In addition to infections, some tumours could trigger this type of immune reaction, because tumours often have clusters of cells undergoing abnormal cell death at their core as they feed off a limited blood supply. This immune reaction helps the body fight cancer cells.

Dr Caetano Reis e Sousa, lead author based at Cancer Research UK's London Research Institute, said: "After a 15 year hunt, we've identified the first 'danger receptor' - one which senses abnormal cell death and then triggers an immune response.

"The detection of 'danger' could explain some situations when a tumour triggers an immune reaction against itself."

The receptor, called DNGR-1, is found on dendritic cells. Dendritic cells are messengers that instruct other immune cells - known as T cells - to attack foreign invaders.

Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "The concept of using the body's immune system to fight cancer has been around for decades, but advances in recent years have made this field of research a very exciting one.

"The results of this study are really important scientifically and a step towards understanding how to manipulate the immune system to treat cancer in the future."

* Sancho D, Joffre OP, Keller AM, Rogers NC, Martínez D, Hernanz-Falcón P, Rosewell I, E Sousa CR. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature; doi:10.1038/nature07750

For the full press release and other Cancer Research UK news and press releases, see online News.

For more information on Caetano Reis e Sousa and the Immunobiology Laboratory, see his research profile.