Scientists are working on a “breakthrough” cancer vaccine after discovering how the body’s immune system targets cells devastated by the disease, according to the researchers from the University of Southampton.
Their study has found that the body’s natural “killer” cells – from the immune system which protects against disease and infections – instinctively recognise and attack a protein that drives cancer growth, reports The Independent.
They believe that by using this protein, XPO1, they may be able to activate more killer cells to destroy the disease, paving the way for new and less invasive forms of cancer treatment.
Professor of hepatology Salim Khakoo, lead author of the study published in the Science Advances journal, 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.
“Killer cells are an emerging form of immunotherapy that shows huge promise. They don’t attack healthy tissue in the way chemotherapy and other immunotherapies do, so are safer and have fewer side effects than traditional forms of cancer treatment.”
He said the XPO1 protein is essential for normal cell function but 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, triggering 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,” added Khakoo.
“This holds true for a range of cancers including those with higher rates of death like liver cancer, which has an average survival rate of only 18 months.
“As well as liver cancer, killer cell treatment in the future could be used to treat head and neck cancers, endometrial, bladder or breast cancer.”
A University of Southampton spokesman said previous studies had linked natural killer cells to the body’s protection against cancer, but the latest study is the first to highlight a viable technique of activating killer cells by targeting the XPO1 protein to fight the disease.
Co-author Professor Ralf Schittenhelm, from Monash University in Australia, 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.
“The potential to develop targeted therapies that utilise the body’s own immune system is incredibly exciting.”
The team is now working on the development of the world’s first vaccine that uses natural killer cells to fight cancer.
Study details
The nuclear export protein XPO1 provides a peptide ligand for natural killer cells
Matthew Blunt, Hayden Fisher, Ralf Schittenhelm, Berenice Mbiribindi, Salim. Khakoo et al.
Published in Science Advances on 23 August 2024
Abstract
XPO1 (Exportin-1/CRM1) is a nuclear export protein that is frequently overexpressed in cancer and functions as a driver of oncogenesis. Currently small molecules that target XPO1 are being used in the clinic as anticancer agents. We identify XPO1 as a target for natural killer (NK) cells. Using immunopeptidomics, we have identified a peptide derived from XPO1 that can be recognised by the activating NK cell receptor KIR2DS2 in the context of human leukocyte antigen–C. The peptide can be endogenously processed and presented to activate NK cells specifically through this receptor. Although high XPO1 expression in cancer is commonly associated with a poor prognosis, we show that the outcome of specific cancers, such as hepatocellular carcinoma, can be substantially improved if there is concomitant evidence of NK cell infiltration. We thus identify XPO1 as a bona fide tumour antigen recognised by NK cells that offers an opportunity for a personalised approach to NK cell therapy for solid tumours.
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