Scientists Unveil How Killer Cells Target Cancer

Monash University

An international team of scientists are on the verge of a cancer breakthrough after working out how the body's immune system targets cells devastated by the disease.

A new study published in the journal Science Advances has discovered that our natural killer cells, from the immune system which protect against disease and infections, instinctively recognise and attack a protein that drives cancer growth.

The experts say that by hijacking this protein, known as XPO1, they may be able to activate more killer cells to destroy the disease.

The study authors – led by Professor of Hepatology Salim Khakoo, from the University of Southampton in the UK and co-authored by Professor Ralf Schittenhelm, and Professor Anthony Purcell from the Monash Biomedicine Discovery Institute in Australia – believe it could offer new and less invasive forms of treatments.

Professor Ralf Schittenhelm said the discovery could change the course of immunotherapy.

"We hope it could lead to personalised cancer treatment, especially in cases where traditional therapies have failed," Professor Schittenhelm said.

"The potential to develop targeted therapies that utilise the body's own immune system is incredibly exciting."

Professor Salim Khakoo said it was previously believed that killer cells attack cancer cells in a random manner.

"Our findings actually show how our body's immune system recognises and attacks these cancer cells," Professor Khakoo said.

"Killer cells are an emerging form of immunotherapy that show huge promise.

"They don't attack healthy tissue in the way chemotherapy and other immunotherapies do, so are safer and have less side-effects than traditional forms of cancer treatment."

The XPO1 protein examined by the scientists is essential for normal cell function.

However, in many cancers, it becomes overactive and allows malignant cells to multiply unchecked.

The scientists found that a peptide – short chains of amino acids – derived from the XPO1 protein attracted the natural killer cells.

They said this triggers the body's immune response against the cancerous cells.

"Patients with cancer who had both active killer cells and high levels of XPO1 had significantly better survival rates," Professor Khakoo said.

"This holds true for a range of cancers including those with higher rates of death such as liver cancer, which has an average survival rate of only 18 months.

"As well as liver cancer, natural killer cell treatment in the future could be used to treat head and neck cancers, endometrial, bladder or breast cancer."

Professor Anthony Purcell said: "This finding builds on decades of antigen discovery research that incorporate state-of-the-art mass spectrometry instrumentation for the identification of novel immune targets. We wait with excitement to see how these targets progress to the clinic and benefit cancer patients."

Previous studies have linked natural killer cells to the body's protection against cancer.

But this latest study is the first of its kind to highlight a viable technique of activating killer cells – to target the XPO1 protein – to fight the disease.

The team is now working on the development of the world's first vaccine that uses natural killer cells to fight cancer.

Read the full paper in Science Advances: The nuclear export protein XPO1 provides a peptide ligand for natural killer cells. DOI: 10.1126/sciadv.ado6566

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