Prior Heart Disease Increases Risk of ICI-Associated Myocarditis

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy used in cancer. However, in rare cases, they cause a kind of myocarditis called immune checkpoint inhibitor-associated myocarditis (ICI-associated myocarditis).

A new study, which received funding by the Global Autoimmune Institute, examined the role of tissue-resident memory T cells in ICI-associated myocarditis. This type of T cell remains in tissues and provides a fast-acting defense against invaders they’ve encountered before. However, problems arise when these cells target our own bodies.

The researchers found that cardiac injury triggers the recruitment of self-reactive tissue-resident memory T cells that target cardiac myosin to the heart. Because these cells have a large amount of a molecule called PD-1 on their surface, they can be activated by anti-PD-1 blocking antibodies, a type of immune checkpoint inhibitor used to treat cancer. 

Normally, PD-1 acts as an “off switch” for T cells so anti-PD-1 blocking antibodies help T cells remain active to target cancer cells. However, when these therapies interact with self-reactive T cells, such as myosin-targeting T cells, they inadvertently activate T cells targeting the heart leading to ICI-associated myocarditis.

Citation:

Kalinoski, H. et al. Injury-induced myosin-specific tissue-resident memory T cells drive immune checkpoint inhibitor myocarditis. PNAS 121 (42) e2323052121 (2024). DOI: 10.1073/pnas.2323052121