Myocarditis in cancer patients is driven by specific immune cells

Myocarditis is an inflammatory process of the myocardium. In most of the developed countries, viral infections are most frequently the cause of myocarditis. While in developing countries, rheumatic carditis, Chagas disease, and complications related to advanced HIV/AIDS also provide important causes of myocarditis. Other causes include toxic myocarditis, which is related to drugs that may cause an insidious form of the disease.

In a new study, researchers from UC San Francisco and Vanderbilt University Medical Center have identified specific immune cells that drive deadly heart inflammation in a small fraction of patients treated with powerful cancer immunotherapy drugs.

The researchers also identified the cells in heart muscle that is targeted by the destructive immune cells, and their new findings already have led them to begin investigating better ways to prevent or treat this potentially lethal heart inflammation. The form of myocarditis they studied is an infrequent but deadly side effect of cancer immunotherapy drugs called immune checkpoint inhibitors (ICIs).

The new study, published in Nature, reports ability to mimic human immune checkpoint inhibitors -caused myocarditis . in the new study, the researchers used a strain of mice in which the same proteins targeted by immune checkpoint inhibitors in humans were instead genetically knocked-out. They found that immune system cells called CD8 T lymphocytes predominate in inflamed heart tissue of mice afflicted with myocarditis.

These same activated T cells are necessary to trigger myocarditis in immune checkpoint inhibitors -treated cancer patients, and therefore immunosuppressive therapies that affect CD8 T cells might play a beneficial role.

Reference:

Axelrod, M.L., Meijers, W.C., Screever, E.M. et al, T cells specific for α-myosin drive immunotherapy-related myocarditis, Nature (2022), DOI: 10.1038/s41586-022-05432-3.