Single-cell transcriptomic insights into the immune heterogeneity of immune checkpoint inhibitors related organ toxicities

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, but their increasing clinical use has led to an increasing incidence of immune-related adverse events (irAEs), among which colitis and cardiotoxicity are particularly severe, compromising both quality of life and therapeutic outcomes. Recent advances in single-cell RNA sequencing (scRNA-seq) have enabled high-resolution profiling of immune cell heterogeneity, offering new insights into the mechanisms of irAEs. By dissecting immune cell phenotypes and interactions across affected organs, scRNA-seq helps to clarify the pathogenesis of toxicity and supports the development of personalized immunomodulatory strategies. In this review, we summarize the clinical features, underlying mechanisms, and immune landscape of ICI-associated colitis and cardiotoxicity. Through comparative analysis, we highlight shared mechanisms-such as T cell clonal expansion, IFN-γ/IL-1β-driven inflammatory circuits, and JAK-STAT signaling-as well as organ-specific features, including microbiota-dependent regulation in colitis and autoantigen-initiated responses in myocarditis. We also explore emerging therapeutic targets and biomarkers identified by scRNA-seq and discuss their application in other irAEs, such as pneumonitis. Together, this work underscores the value of single-cell technologies in elucidating irAE heterogeneity, advancing irAEs management from reactive response to precise prevention, and guiding future translational research.