Research Press Release

Cancer mutation levels may predict immunotherapy outcomes

Nature Genetics

January 15, 2019

Mutation levels in cancer cells are related to the likelihood of patient survival after checkpoint-inhibitor therapy, reports a large study published online this week in Nature Genetics. The findings suggest that this phenomenon occurs across many cancer types and therefore may help predict which patients will respond well to this form of immunotherapy.

Immune-checkpoint inhibitors are used to stop certain cancers from suppressing the body’s immune response that would otherwise help combat the disease. However, outcomes of this type of immunotherapy vary. Understanding exactly how different patients will respond to immunotherapy remains an important goal of clinical cancer care.

Timothy Chan, David Solit, Luc Morris and colleagues assessed clinical and genomic data from 1,662 patients with advanced cancer who had been treated with immune-checkpoint inhibitors as well as 5,371 patients who had not.

The authors sequenced a panel of cancer-related genes in tumors from patients with metastatic disease and quantified the extent to which each patient’s tumours had mutated (also known as ‘tumour mutational load’). They found that patients with tumors that had mutated more extensively had better overall survival rates after checkpoint-inhibitor immunotherapy. However, different cancer types appeared to have different levels of mutation thresholds associated with an improved likelihood of survival.

These findings suggest that tumour mutational load may prove to be a useful metric to predict a patient’s response to checkpoint-inhibitor immunotherapy across different cancer types.

DOI:10.1038/s41588-018-0312-8 | Original article

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