Peripheral immune mapping and multi-omics analysis in PD-1 inhibitor-induced myocarditis.

Abstract

More immune-related adverse events (irAEs) have emerged along with increased immune checkpoint inhibitors (ICIs) treatment. ICIs-induced myocarditis is a rare type of irAEs with early onset, rapid progression and high mortality. Its specific pathophysiological mechanism is not fully understood. Totally 46 patients with tumor and 16 ICI-induced myocarditis were included. We performed single cell RNA sequencing (scRNA-seq) on CD3+T cells, flow cytometry, plasma analysis of 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 scRNA-seq and performed comparative analysis and further verification. The composition of T cells in the peripheral blood (PB) of patients has changed remarkably. Compared to non-irAEs patients, effector T cells were increased in irAE patients, while naive T cells, γδ T cells and MAIT cells were decreased. Besides, reduced γδ T cells characterized with effector functions, increased NKT cells with high level 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 cell driven by PD-1 inhibitor-induced myocarditis, as well as illustrate clinical features and multiomic characteristics, providing a unique perspective on disease progression and therapy in clinical practice.