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Immunotherapy is a promising form of treatment that strengthens a patient’s own immune system as a way to fight cancer. Some forms of cancer, particularly melanoma, respond well to immunotherapy, but despite its promise, only about one-third of people with melanoma actually see their tumours shrink as a result. Further, immunotherapy is expensive and can cause significant side effects, so ideally doctors would only offer it to patients who will benefit.
To address this challenge, researchers have been looking for unique biological features on tumours that act like signatures to identify people who will respond to immunotherapy. As an added bonus, these signatures may also predict the long-term outcomes of patients.
Two recent studies published in the same issue of the journal Nature Medicine describe different signatures with potential to identify people with melanoma who will benefit from immunotherapy. They used different strategies to find the signatures, but both may be valuable for predicting treatment success.
Neuroblastoma features may predict success in melanoma
In one study, researchers developed a model that could predict immunotherapy response in melanoma based on information from a very different type of cancer – neuroblastoma. Neuroblastoma is a childhood nervous system cancer, and it is somewhat unusual among childhood cancers in that tumours in some patients shrink in response to immune attacks, with or without help from immunotherapy.
The researchers identified a set of 15 genetic features that, when present, indicated that the neuroblastoma tumour would respond to the immune system. They then looked for these same genetic features in melanomas. The more of these features that they shared with neuroblastoma, which they called an IMPRES score, the better the melanoma responded to immunotherapy. They found that the score reliably predicted whether melanoma would respond to immunotherapy and could even forecast a patient’s overall survival.
How tumours avoid immune attack may help identify patients
In the other study, a different research team found another way to predict immunotherapy success in melanoma by looking at the genetics behind why an immune attack fails.
In some cases, immune cells are not able to invade tumours to attack individual cancer cells; in others, immune cells can invade but don’t work properly when they get there and fail to attack cancer cells. The researchers looked for genetic features behind either of these problems and identified a signature that combined these genetic features, creating a score that they called TIDE.
They tested the value of TIDE in a few cancers and found that this signature was able to accurately predict whether a melanoma would respond to widely used immunotherapies. It was also associated with patient survival and could help to predict if a patient would become resistant to immunotherapy.
Genetic signatures provide valuable information before treatment
For many types of treatment, especially those associated with significant costs and side effects, doctors and patients want to know whether the treatment will be effective before it starts. These predictive tools don’t exist for immunotherapy yet, but these two studies have made significant progress toward that goal.
The two different scores looked at different biological features of tumour cells to predict how a patient will fare on immunotherapy. Each shows that a unique set of genes are behind the tumour response, which can be exploited to identify patients who can benefit from this treatment. This may be valuable for a number of cancers, but particularly melanoma, where responses can be so variable.
Eileen Hoftyzer, BSc