Genetic changes in tumours may predict who will respond to immunotherapy

In collaboration with the Press Association

Researchers have discovered genetic changes in tumours that could be used to predict who will benefit from immunotherapy.

As well as being used to determine individuals who may respond well to this type of treatment, this information could also help identify who should be presented with other options, before treatment begins.

Michelle Mitchell, chief executive of Cancer Research UK, said it’s fantastic to think of a future where people have a simple test before they start their immunotherapy to find out if it’s the right course of treatment for them. 

“This not only will spare patients from taking needless treatment and enduring serious side effects that might come with it, but it could also save the NHS treatment costs.”

The new research, published in the journal Cell, was led by researchers at the Francis Crick Institute, UCL Cancer Institute and the Cancer Research UK Lung Cancer Centre of Excellence and partly funded by Cancer Research UK.

The largest study of its kind

Immunotherapy, a treatment that helps the immune system to recognise and attack cancer cells, has made considerable progress as an approach to treating certain types of cancer. But a big challenge has been that only a subset of people’s cancers respond to it – something that scientists have been keen to understand. 

“Checkpoint inhibitors are really valuable in treating a number of cancers, including skin and lung cancers. But sadly, they do not always work and they can also sometimes cause severe side effects.”Professor Charles Swanton, chief clinician at Cancer Research UK and group leader at the Francis Crick Institute and UCL

In the latest study, the team looked at genetic changes in the tumours of over 1,000 patients being treated with a specific type of immunotherapy that stops cancer cells from shutting down the body’s immune response – known as checkpoint inhibitors.

Dr Kevin Litchfield, a visiting scientist at the Crick and group leader at UCL said the study was the largest of its kind, analysing genetic and gene expression data from across 7 cancer types and over a thousand people.

More informed treatment decisions

One key finding from this ambitious study was that the total number of genetic changes (mutations) present in every cancer cell was the best predictor of tumour response to immunotherapy. The more mutations in every tumour cell, the higher the chances it would respond well to treatment. In addition, the expression of a particular gene, CXCL9, was identified as a critical driver of an effective anti-tumour immune response.  

On the other hand, having more copies of a gene called CCND1 was linked to tumours being resistant to immunotherapy.

Litchfield, who led the study alongside Swanton, said that as well as pinpointing the specific genetic factors that determine if a tumour responds to immunotherapy, the study also improved their understanding of how immunotherapy works, which is vital for the design and development of new improved immunotherapies.

The researchers are now working with clinical partners in Denmark to see if the test they developed correctly identifies who will or will not respond to checkpoint inhibitors and if it’s more accurate than currently available tests. 

Swanton is excited by the potential of the findings. “If doctors have an accurate test, that tells them whether these drugs are likely to be effective in each individual patient, they will be able to make more informed treatment decisions,” he said. “Crucially, they will be able to more quickly look for other options for patients who these drugs are unlikely to help.” 

References

Litchfield, K et al. (2020) Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition. Cell. DOI:https://doi.org/10.1016/j.cell.2021.01.002