A NEW Oxford study has identified a genetic marker that could be used to predict a patient's risk of developing serious side-effects when undergoing immunotherapy treatment for one of the most common skin cancers.

The study, which was supported by the NIHR Oxford Biomedical Research Centre (BRC), analysed genetic information from more than 200 patients undergoing treatment for melanoma, to find stretches of DNA that correlated with whether the patient developed severe side-effects from the treatment.

The findings, which were partly based on samples given by skin cancer patients at the Churchill Hospital, were published in the journal Nature Medicine.

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Cancer immunotherapy is central to the medical management of melanoma, being used to reduce the risk of melanoma returning after surgery, but also when it has spread around the body.

The most common immunotherapy involves patients being given drugs called 'checkpoint inhibitors', which help stimulate the immune system and are given as infusions through a drip.

While checkpoint immunotherapy has revolutionised melanoma treatment, a subset of patients will develop serious side-effects due to their immune system attacking other tissues and organs.  This can lead to diverse symptoms, including diarrhoea, lung inflammation and joint and muscle pain. 

Currently clinicians have no way of predicting who will develop such side-effects and have very limited insights into the way side-effects develop.

In this latest research a study from the Dana Faber Cancer Institute, co-published in Nature Medicine, found that patients who carried a change in the genetic code of the IL7 gene were significantly more likely to develop side-effects.

The paper from the Oxford team, led by Associate Professor Ben Fairfax from the MRC Weatherall Institute of Molecular Medicine at the University of Oxford, was able to replicate the Dana Faber findings, and extended the work by showing the immunological consequences of this change.

Professor Fairfax said: "We found individuals carrying this genetic variant, which is present in about eight percent of patients treated for melanoma, were about six times more likely to develop side-effects severe enough to require steroids.

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"Furthermore, we found this genetic variant alters the amount of IL7 code produced by B cells - a cell type normally associated with making antibodies, so to see the genetic effect acting in these cells was surprising."

The Oxford researchers found that the effect of this genetic change was detectable in B cells before immunotherapy was given, suggesting B cells play an important role in the immune response to untreated skin cancer.

Professor Fairfax said: "What is fascinating is that whilst patients with this genetic risk variant were more likely to get side-effects from immunotherapy, both groups found that patients with this change appeared independently to have less chance of the cancer returning."

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This story was written by Anna Colivicchi, she joined the team this year and covers health stories for the Oxfordshire papers. 

Get in touch with her by emailing: Anna.colivicchi@newsquest.co.uk

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