How natural killer cells detect and destroy

Researchers have made inroads into better understanding the cytotoxic capacity of natural killer cells (NK cells) and hope to translate this into tackling cancers and other disorders.

Dr Nick Huntington, Dr Priyanka Sathe and Ms Rebecca Delconte from the Walter and Eliza Hall Institute in Melbourne found that the MCL-1 protein is essential for the survival of NK cells. They suggest that MCL-1 could be a target for boosting or depleting NK cell populations to treat disease.

NK cells are immune predators, scouring the body in search of foreign invaders such as viruses and sensing changes in the body’s cells that are associated with cancer.

Huntington said the team showed NK cells were needed to fight off invading tumour cells that had spread past the original cancer site - such as melanoma cells that have spread to the lungs.

“We discovered MCL-1 is absolutely essential for keeping natural killer cells alive,” Huntington said. “Without natural killer cells, the body was unable to destroy melanoma metastases that had spread throughout the body, and the cancers overwhelmed the lungs.

“Knowing how important natural killer cells are for detecting and destroying cancer cells as they spread suggests they would be a good target for boosting immune defences to treat cancer.”

The researchers showed that MCL-1 levels inside the cell increased in response to the cytokine, interleukin 15 (IL-15). Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner.

“We previously knew IL-15 boosted production and survival of natural killer cells, and we have shown that IL-15 does this by initiating a cascade of signals that tell the natural killer cell to produce MCL-1 to keep it alive,” said Huntington.

Natural killer cells are present in high frequency in the blood acting at the ‘frontline’ of defence - the lungs, intestines, mucous membranes and skin - to detect and destroy diseased cells. However, these predatory natural killer cells are a double-edged sword.

Huntington said the team also found natural killer cells were critical to the body’s rejection of donor bone marrow transplants and in the runaway immune response during toxic shock syndrome.

“Natural killer cells led the response that caused rejection of donor stem cells in bone marrow transplantations,” Huntington said. “They also produced inflammatory signals that can result in toxic shock syndrome, a potentially fatal illness caused by bacterial toxins that causes a whole-body inflammatory reaction.”

Huntington said the discovery provided a solid lead to look for ways of boosting natural killer cells when they are needed in higher supply or depleting them when they are causing illness.

The  research has been published in Nature Communications