Liquid Biopsy Test Enables Early Detection of ICI-Related Myocarditis

Immune checkpoint inhibitors (ICIs), which have transformed cancer therapy, can cause a rare and deadly heart condition known as myocarditis, with a mortality rate as high as 40%. Early detection of ICI-related myocarditis is essential to adjust treatment and reduce risks, but diagnosis has been challenging since imaging and tissue biopsy methods are either insufficient or invasive. Now, a new blood-based diagnostic approach offers a promising solution to identify the condition earlier and more safely.

Researchers at the Stanford Cardiovascular Institute (Stanford, CA, USA) have developed a liquid biopsy technique using cell-free mRNA to detect myocarditis related to cancer immunotherapy. Unlike traditional liquid biopsy methods that rely on protein markers, cfDNA, or miRNA, this technique enables tissue- and cell type-specific profiling of gene expression from a simple blood draw. It can detect cell-free mRNA from both immune cells attacking the heart and from damaged heart muscle tissue, allowing precise identification of inflammation and injury caused by cancer treatment.

The team validated the method in a study involving 22 patients who developed myocarditis after receiving ICI therapy. The researchers consistently retrieved sufficient mRNA from blood samples to conduct detailed analyses, proving the approach’s feasibility. They also identified a panel of genes that were significantly upregulated in myocarditis patients compared to healthy controls. Using machine learning models, the researchers enhanced their ability to distinguish gene expression changes associated with myocarditis.

The findings, published in the Journal of Clinical Investigation, demonstrate that liquid biopsies using cell-free mRNA can detect both immune-related reactions and cardiac tissue damage in cancer patients receiving immunotherapy. This approach provides a minimally invasive and highly sensitive diagnostic tool for identifying treatment-related side effects earlier. In the future, the technology could be expanded for broader use in monitoring patients receiving other cardiotoxic treatments, enabling earlier interventions and better outcomes.

Related Links:
Stanford Cardiovascular Institute