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New results about immunotherapy in hereditary melanoma
Researchers at Karolinska Institutet have examined how effective immunological checkpoint therapy is for individuals with inherited CDKN2A mutation and metastatic melanoma.
In recent years, new immunological treatments have appeared that many melanoma patients respond well to. These, so called immune checkpoint inhibitors treat cancer by inhibiting brake mechanisms in the immune system, a discovery by James P. Allison and Tasuku Honjo, for which they are now awarded the 2018 Nobel Prize in Physiology or Medicine.
Good news
“We saw that the mutation-carriers with metastatic melanoma responded surprisingly well to immunotherapy,” says study leader Hildur Helgadottir at the Department of Oncology-Pathology, Karolinska Institutet. “This is good news, particularly for this otherwise vulnerable patient group.”
Almost two-thirds of the 19 patients with CDKN2A mutations included in the study responded to the treatment in a way that the tumours shrank or, as was the case in a third of the patients, disappeared completely. The expected response going by earlier studies was that just over one third would respond to the treatment and that the tumours would disappear in only one in fifteen patients. The researchers also discovered that melanoma tumours with CDKN2A mutation had a larger number of mutations compared to tumours with no CDKN2A mutation. A possible explanation for the good therapeutic efficacy, according to the researchers, is that CDKN2A mutated tumour cells with many mutations become so unlike healthy cells that the immune system finds them easier to recognise as foreign.
“Our conclusion from the study is that CDKN2A mutation carriers with metastatic melanoma have good chances of responding to immunotherapy, which can be associated with the fact that tumours with a CDKN2A mutation seem to have a tendency to accrue even more mutations, although this relationship requires further investigation,” says Dr Helgadottir.
The study was made in cooperation with researchers at Lund University and Gothenburg University in Sweden and researchers in Leiden in Holland, Genua in Italy, Barcelona in Spain and Sidney in Australia.
The study is published in the Journal of Medical Genetics.
Photo of Hildur Helgadottir, researcher at the Department of Oncology-Pathology, Karolinska Institutet: Private
Published: October 10, 2018
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