T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma [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 cellular determinants of severe irAE development, we performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) obtained pretreatment from patients with metastatic melanoma treated with immune checkpoint blockade. ---------------------------------------- Authors state "raw data are not available due to patient privacy concerns".

接受免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）治疗的黑色素瘤患者中，多达60%会发生严重免疫相关不良事件（immune-related adverse events, irAEs）。然而，目前尚不清楚是否存在共同的基线免疫状态先于免疫相关不良事件的发生。本研究利用质谱流式细胞术（CyTOF）、单细胞RNA测序（single-cell RNA sequencing）、批量RNA测序（bulk RNA sequencing）以及T细胞受体测序（T cell receptor sequencing），对接受免疫检查点抑制剂治疗的转移性黑色素瘤患者的治疗前外周血样本进行分析，旨在探究与严重免疫相关不良事件发生相关的细胞因素，且不局限于受累器官系统。研究结果证实了与免疫检查点抑制剂诱导的毒性相关的循环T细胞特征，这对优化诊断及临床管理具有参考意义。为探究严重免疫相关不良事件发生的细胞决定因素，我们对接受免疫检查点阻断治疗的转移性黑色素瘤患者的治疗前外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）开展了单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）。作者声明："由于患者隐私保护问题，原始数据无法公开。"