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

ABSTRACT:

Background

Immune checkpoint inhibitor (ICI) therapies present a pillar of modern cancer therapy but can cause neurological immune-related adverse events (n-irAEs), of which up to 35% are severe or even fatal. However, the detailed immunological mechanisms and risk factors underlying n-irAEs remain largely unknown. Here, we leveraged single-cell genomics to dissect immune cell type, state, and clonal heterogeneity associated with n-irAEs.

Methods

We performed coupled single-cell RNA sequencing and T cell receptor (TCR) profiling on peripheral blood cells of 17 patients with cancer receiving ICI therapy, including 8 patients with acute neurotoxicity. This approach enabled integrated analyses of immune cell states and T cell clonality linked to ICI-induced n-irAEs.

Results<

SUBMITTER: Giguelay AM 

PROVIDER: S-EPMC12574404 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature