A recent study has provided evidence for a molecule in the immune system that can kill genetically diverse cancer cells without harming healthy cells, raising the possibility of harnessing it for a novel anti-cancer therapy.
The innate immune system, which is present from birth, is a network of biological processes that are critical for fighting disease. The system has evolved to combat genetically diverse pathogens and limit host toxicity. However, it is largely unknown whether the innate immune system can protect the body from cancer.
Recently, researchers at the University of Chicago Medicine Comprehensive Cancer Centre (UChicago) explored the possibility that the innate immune system could, in fact, fight cancer in humans. The team aimed to reveal cancer’s ‘weak spot’ and subsequently drive the development of more effective treatments with fewer side effects. Remarkably, they did just that – the researchers have now uncovered an innate molecule that could kill cancer cells!
Polymorphonuclear neutrophils (PMNs) are a type of white blood cell found in the innate immune system of humans. Historically, it was understood that PMNs were involved in the killing of cancer cells. Yet, until now, the exact mechanisms behind this line of defence remained largely unknown.
The team of researchers at UChicago managed to identify a major anti-cancer protein, called neutrophil elastase (ELANE), which they found was released by PMNs. The properties of ELANE made this discovery even more significant. The team found that ELANE only activated cell death pathways in cancer cells, within tumours or at distant locations, leaving nearby healthy cells intact.
Below is the cancer-killing program:
- PMNs secrete ELANE.
- This liberates the CD95 death domain. This is a system that is responsible for keeping the immune system balanced and for controlling which cells undergo cell death.
- The activated CD95 death domain interacts with histone H1, which is elevated in cancer cells. This selective interaction is what allows ELANE to only kill cancer cells.
It was found that ELANE consistently activated this pathway in many types of cancer cell lines. Also, it was suggested that ELANE’s specificity for cancer cells was likely to limit potential toxicity and preserve immune cells. This in turn would allow antigens to generate a boosted immune response at sites where the cancer had spread.
These profound findings have the potential to aid the development of novel medicines designed to select target cancer cells and spare nearby healthy cells. The researchers validated ELANE’s efficacy across nine types of genetically diverse cancers, including those that are difficult to treat. As it has been shown that ELANE can kill a vast range of cancer cells, the scope for possible treatment options in the future is extremely broad.
Lev Becker, a lead researcher involved in the project at UChicago, explained:
“Taking a step back, what I think we’ve stumbled upon is our body’s first response to mutated cells. Cells are constantly changing, and mutations accumulate. Some people develop cancer, others do not. The pathway that we’ve discovered may help explain the primordial mechanisms of our immune system to eliminate those mutated cells.”
Following on from these exciting discoveries, future research is now required to learn how to maximise ELANE’s therapeutic effects – this may involve combining this molecule with existing cancer treatments. If successful, the use of ELANE may improve the practise of precision medicine regarding cancer therapies and positively impact an enormous number of patients.
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