The study, published in Nature Medicine, analysed genetic information from more than 200 patients undergoing treatment for melanoma (one of the most common skin cancers), to find stretches of DNA that correlated with whether the patient developed severe side-effects from the treatment.
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. Whilst 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. Whilst these are typically transient, patients may require strong steroid medication to dampen their immune responses and often have to stop immunotherapy altogether. In rare cases these side-effects can be life-threatening. Currently clinicians have no way of predicting who will develop such side-effects, and also 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, identified a change in the genetic code of the IL7 gene - with patients carrying this 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.