Whole exome sequencing predicts whether patients respond to cancer immunotherapy: A two-step approach with sequencing of 20,000 genes improves prediction of who benefits from immune checkpoint inhibitors

Immunotherapies, such as immune checkpoint inhibitors, have transformed the treatment of advanced stage cancers. Unlike chemotherapies that kill cancer cells, these drugs help the body’s immune system to find and destroy cancer cells themselves. Unfortunately, only a subset of patients responds long-term to immune checkpoint inhibitors — and these treatments can come at a high cost and with side effects.

Researchers have developed a two-step approach using whole exome sequencing to zero in on genes and pathways that predict whether cancer patients will respond to immunotherapy. The study, published in Nature Communications and conducted by researchers at New York University, Weill Cornell Medicine, and the New York Genome Center, illustrates how the use of whole exome sequencing can better predict treatment response than current laboratory tests.

“Can we better predict who will benefit from immunotherapy? Scientists have developed various biomarkers that help anticipate immunotherapy treatment response, but there’s still an unmet need for a robust, clinically practical predictive model,” said Neville Sanjana, assistant professor of biology at NYU, assistant professor of neuroscience and physiology at NYU Grossman School of Medicine, a core faculty member at New York Genome Center, and the study’s co-senior author.

Several biomarkers — including age, tumor type, and the number of mutations found in cancer cells, known as tumor mutational burden — are already known to correlate with responses to immunotherapy. Tumor mutational burden, which is calculated by analyzing a few hundred genes, is the most well-established predictor and is often used to determine a patient’s eligibility for immune checkpoint inhibitors.

If scientists look at a much larger portion of our genes, could that help to better predict which patients will respond to immunotherapy? Whole exome sequencing is a method for sequencing the part of the genome that codes for proteins — around 20,000 genes, or two percent of the genome — to look for mutations that may be involved in disease.

While whole exome sequencing is not widely used in cancer treatment, some recent studies of immunotherapies have started to include sequencing. These studies are small, but together can help illuminate the relationship between genomic factors and how patients respond to immunotherapy.

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