T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [BCR and TCR scRNA-Seq]

Severe immune-related adverse events (irAEs) occur in up to 60% of melanoma patients treated with immune checkpoint inhibitors (ICIs). However, it remains unknown whether a common baseline immunological state precedes irAE development. Leveraging CyTOF, single-cell RNA sequencing, bulk RNA sequencing, and T cell receptor sequencing to analyze pretreatment blood from metastatic melanoma patients treated with ICIs, we investigated cellular factors associated with severe irAE development regardless of organ system involvement. Our results demonstrate circulating T cell characteristics associated with ICI-induced toxicity, with implications for improved diagnostics and clinical management. To investigate the association of TCR and BCR diversity with severe irAE development, we performed single-cell V(D)J sequencing (scVDJ-seq) on peripheral blood mononuclear cells (PBMCs) obtained pre-treatment from patients with metastatic melanoma. ---------------------------------------- Authors state "raw data are not available due to patient privacy concerns".