Work

Distinct immune cell dynamics associated with immune-related adverse events during combined chemoradiation and immune checkpoint inhibitor therapy

Year: 2025

Type: article

Abstract: Combining chemoradiotherapy with immunotherapy increases the risk of immune-related adverse events (irAEs), but the underlying mechanisms remain poorly understood. To address this, we conducted a longitudinal single-cell multi-omics analysis of patients with locally advanced cervical cancer. Here we show that the proportions of CD4+ and CD8+ terminally differentiated effector memory or effector T cells are elevated in patients with irAEs. Chemoradiotherapy reduces B cell clonality while increasing the abundance and somatic hypermutation frequencies of IgA+ and IgG+ B cells in irAE patients. In the myeloid compartment, combined treatment expands specific monocyte subclusters associated with irAEs. Spatial transcriptomics and immunofluorescence analyses further reveal that these irAE-associated immune cells aggregate within the tumor microenvironment. Finally, we develop the predictive models for irAEs and integrate them, along with all datasets, into a user-friendly data portal. Our findings suggest that chemoradiotherapy and immunotherapy exert distinct effects on different immune cells, contributing to irAE development. The mechanisms underlying immunerelated adverse events (irAEs) following the combination of chemoradiotherapy with immunotherapy remain to be characterized. Here, single cell multi-omics and spatial transcriptomics on locally advanced cervical cancer patients identifies distinct effects on different immune cells associated with irAEs.

Source: Nature Communications

DOI: 10.1038/s41467-025-67689-2