Researchers at the Francis Crick Institute, the UCL Cancer Institute, and the Cancer Research UK Lung Cancer Centre of Excellence have identified genetic changes in tumours which could be used to predict if immunotherapy drugs would be effective in individual patients.
Immunotherapies have led to huge progress in treating certain types of cancer, but only a subset of patients respond. The challenge for doctors and researchers is in understanding why they work in some people and not others, and in predicting who will respond well to treatment.
In their paper, published in Cell (27 January), the scientists looked for genetic and gene expression changes in tumours in over 1,000 patients being treated with checkpoint inhibitors, a type of immunotherapy which stops cancer cells from switching off the body’s immune response.
They found that the total number of genetic mutations which are present in every cancer cell in a patient was the best predictor for tumour response to immunotherapy. The more mutations present in every tumour cell, the more likely they were to work. In addition, expression of gene CXCL9 was found to be a critical driver of an effective anti-tumour immune response.
The researchers also looked at the cases where checkpoint inhibitors had not been effective. For example, having more copies of a gene called CCND1 was linked to tumours being resistant to checkpoint inhibitors. More research is needed, but the scientists suggest that patients with this mutation in their tumours may benefit more from alternative drug treatment options.
Kevin Litchfield, co-lead author of the Cell paper and group leader of the Tumour Immunogenomics and Immunosurveillance lab at UCL said: “It has enabled us to pinpoint the specific genetic factors which determine tumour response to immunotherapy and combine them into a predictive test to identify which patients are most likely to benefit from therapy. Furthermore, it has improved our biological understanding of how immunotherapy works, which is vital for the design and development of new improved immunotherapeutic drugs.”
The work was partly funded by Cancer Research UK, the Royal Society, the Wellcome Trust, the Medical Research Council and Rosetrees Trust, among others.