Cardiac injury recruits autoreactive myosin-specific tissue-resident memory T cells, increasing susceptibility to immune checkpoint inhibitor myocarditis upon anti-PD-1 treatment.
Does prior cardiac injury increase susceptibility to immune checkpoint inhibitor-associated myocarditis via recruitment of myosin-specific tissue-resident memory T cells?
Prior cardiac injury recruits myosin-specific tissue-resident memory T cells to the heart, increasing susceptibility to immune checkpoint inhibitor-associated myocarditis.
Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor–associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (T RM ) cells, we characterized cardiac T RM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia–reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC T RM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC T RM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human T RM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69 + T RM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial T RM cells.
Kalinoski et al. (Tue,) conducted a other in Immune checkpoint inhibitor-associated myocarditis. Cardiac injury followed by anti-PD-1 antibodies was evaluated on Susceptibility to ICI-myocarditis development and characterization of T RM cells. Cardiac injury recruits autoreactive myosin-specific tissue-resident memory T cells, increasing susceptibility to immune checkpoint inhibitor myocarditis upon anti-PD-1 treatment.