Clonally expanded effector CD4+ cytotoxic T lymphocytes are associated with severe neurological adverse events after immune checkpoint inhibitor therapy

Immune checkpoint inhibitor (ICI) therapies present a pillar of modern cancer therapy but can cause severe and potentially fatal neurological immune-related adverse events (n-irAEs). Here, we performed single-cell RNA sequencing and T cell receptor profiling of PBMCs of a cohort of 17 cancer patients receiving ICI therapy. Our data suggest alterations in regulatory T cell frequencies and B cell states, and a significant enrichment of clonally expanded CD4+ cytotoxic T lymphocytes (CD4+ CTLs) with an effector gene expression profile in n-irAE patients.