Abnormal gut microbiota may cause PD-1 inhibitor-related cardiotoxicity via suppressing regulatory T cells.

Treatment with PD-1 inhibitors may cause immune-related adverse events (irAE), of which PD-1 inhibitor-associated myocarditis is a rare and highly lethal irAE. However, the mechanism of PD-1 inhibitors-induced myocarditis in individuals with tumor is still unclear. Regulatory T cells (Treg) can directly inhibit T cell proliferation and activation, and also produce inhibitory cytokines with potent immunosuppressive properties. Deletion or aberrant function of Treg usually leads to autoimmune diseases. But reports on the role of Treg in PD-1 inhibitor-associated myocarditis are still very limited, and its role in the pathogenesis of myocarditis needs to be further explored. In addition, alterations in the composition of the gut microbiota and its metabolites have been shown to be involved in the development of several cardiovascular and autoimmune diseases. Therefore, we designed this experiment initially to investigate the role of gut microbiota in PD-1 inhibitor-associated myocarditis. Our studies showed that PD-1 inhibitors induced myocarditis and significant reduction of intracardiac Tregs in melanoma mice. It is highly likely that alterations in the composition of the gut microbiota due to PD-1 inhibitors played a key role in this process.