Details

Autor(en) / Beteiligte

• Gong, Jingyi
• Neilan, Tomas G
• Zlotoff, Daniel A

Titel

Mediators and mechanisms of immune checkpoint inhibitor-associated myocarditis: Insights from mouse and human

Ist Teil von

• Immunological reviews, 2023-09, Vol.318 (1), p.70-80

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• The broad application of immune checkpoint inhibitors (ICIs) has led to significant gains in cancer outcomes. By abrogating inhibitory signals, ICIs promote T cell targeting of cancer cells but can frequently trigger autoimmune manifestations, termed immune-related adverse events (irAEs), affecting essentially any organ system. Among cardiovascular irAEs, immune-related myocarditis (irMyocarditis) is the most described and carries the highest morbidity. The currently recommended treatment for irMyocarditis is potent immunosuppression with corticosteroids and other agents, but this has limited evidence basis. The cellular pathophysiology of irMyocarditis remains poorly understood, though mouse models and human data have both implicated effector CD8 T cells, some of which are specific for the cardiomyocyte protein α-myosin. While the driving molecular signals and transcriptional programs are not well defined, the involvement of chemokine receptors such as CCR5 and CXCR3 has been proposed. Fundamental questions regarding why only approximately 1% of ICI recipients develop irMyocarditis and why irMyocarditis carries a much worse prognosis than other forms of lymphocytic myocarditis remain unanswered. Further work in both murine systems and with human samples are needed to identify better tools for diagnosis, risk-stratification, and treatment.