T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [bulk RNA-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 cellular determinants of severe irAE development, we performed bulk RNA sequencing (bulk RNA-seq) of peripheral blood mononuclear cell (PBMC) samples obtained at baseline from 61 patients with metastatic melanoma and five healthy controls. The 61 patient samples consisted of two independently profiled bulk cohorts (bulk cohort 1, n = 26; bulk cohort 2, n = 27) and eight patient samples used for technical experiments. >>>Submitter states that raw data will be submitted to dbGaP due to patient privacy concerns<<<