Clonally expanded, thyrotoxic effector CD8⁺ T cells driven by IL-21 contribute to checkpoint inhibitor thyroiditis.

ABSTRACT: Autoimmune toxicity occurs in up to 60% of patients treated with immune checkpoint inhibitor (ICI) therapy for cancer and represents an increasing clinical challenge for expanding the use of these treatments. To date, human immunopathogenic studies of immune-related adverse events (IRAEs) have relied on sampling of circulating peripheral blood cells rather than affected tissues. Here, we directly obtained thyroid specimens from individuals with ICI-thyroiditis, one of the most common IRAEs, and compared immune infiltrates with those from individuals with spontaneous autoimmune Hashimoto's thyroiditis (HT) or no thyroid disease. Single-cell RNA sequencing revealed a dominant, clonally expanded population of thyroid-infiltrating cytotoxic CXCR6⁺ CD8⁺ T cells (effector C

SUBMITTER: Lechner MG 

PROVIDER: S-EPMC10227862 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature