Myocarditis only affects about 1% of patients given immunotherapy, but the mortality rate is 50%. To ameliorate the problem, the scientists dug into the condition and learned that T cells recognize the cardiac antigen α-myosin and attack it (Nature, November 16, 2022). Knowing this, biomarkers can be identified to flag at-risk patients and strategies developed for them to tolerate immunotherapy, the scientists said.

Previous research linked the activity of T cells in the heart to myocarditis and a mouse model was created to replicate what was observed in patients. The team obtained cardiac samples and peripheral blood from three patients with severe myocarditis after receiving immune checkpoint inhibitors. They recreated the condition in mouse models and sequenced individual T cells invading the heart during myocarditis to reconstruct their receptors.

The T-cell receptors were screened against peptides to determine specificity and after analyzing the human samples, the scientists learned the three patients had reactive T cells to the same antigen source, α-myosin, which is expressed only in the heart and skeletal muscles. In other words, the protein α-myosin is a disease-relevant autoantigen in patients with immunotherapy-related myocarditis.