PD-1 inhibitor-induced myocarditis was associated with increased effector T cells, decreased naive and γδ T cells, and exacerbated peripheral inflammatory response compared to non-irAE patients.
Observational (n=62)
What are the peripheral immune and multi-omic characteristics of PD-1 inhibitor-induced myocarditis compared to non-irAE tumor patients?
PD-1 inhibitor-induced myocarditis is characterized by distinct peripheral immune cell shifts, including increased effector T cells and decreased naive and γδ T cells, alongside heightened inflammatory and lipidomic responses.
More immune-related adverse events (irAEs) have emerged along with increased immune checkpoint inhibitor (ICI) treatment. ICI-induced myocarditis is a rare type of irAE with early onset, rapid progression, and high mortality. Its specific pathophysiological mechanism is not fully understood. In total, 46 patients with tumors and 16 patients with ICI-induced myocarditis were included. We performed single-cell RNA sequencing on CD3 + T cells, flow cytometry, proteomics, and lipidomics to improve our understanding of the disease. First, we demonstrate the clinical features of patients with PD-1 inhibitor-induced myocarditis. We then identified 18 subsets of T cells using single-cell RNA sequencing and performed comparative analysis and further verification. The composition of T cells in the peripheral blood of patients has changed remarkably. Compared with non-irAE patients, effector T cells were increased in irAE patients, while naive T cells, γδ T cells, and mucosal-associated invariant T cell cluster cells were decreased. Besides, reduced γδ T cells characterized with effector functions, increased natural killer T cells with high levels of FCER1G in patients may suggest an association with disease development. Meanwhile, the peripheral inflammatory response was exacerbated in patients, accompanied by upregulation of exocytosis as well as increased levels of multiple lipids. We provide a comprehensive overview of the composition, gene profiles, and pathway signatures of CD3+ T cells driven by PD-1 inhibitor-induced myocarditis, as well as illustrate clinical features and multi-omic characteristics, providing a unique perspective on disease progression and therapy in clinical practice.
Gao et al. (Thu,) conducted a observational in PD-1 inhibitor-induced myocarditis (n=62). PD-1 inhibitor-induced myocarditis vs. Non-irAE patients was evaluated on T cell composition and multi-omic characteristics. PD-1 inhibitor-induced myocarditis was associated with increased effector T cells, decreased naive and γδ T cells, and exacerbated peripheral inflammatory response compared to non-irAE patients.