美国斯坦福大学Aaron M. Newman、Aadel A. Chaudhuri等研究人员合作发现，T细胞特征与黑色素瘤患者免疫检查点阻断的毒性相关。相关论文于2022年1月13日在线发表于国际学术期刊《自然—医学》。

研究人员应用飞行时间质谱、单细胞RNA测序、单细胞V(D)J测序、大量RNA测序和大量T细胞受体（TCR）测序来研究了接受抗PD-1单药治疗或抗PD-1和抗CTLA-4联合免疫检查点抑制剂（ICI）治疗黑色素瘤患者的外周血样本。通过分析93个ICI前和早期的血液样本和3个患者队列（n=27、26和18），研究人员发现循环中的2个预处理因素——活化的CD4记忆T细胞丰度和TCR多样性——与严重的irAE发展相关。

研究人员还探讨了接受联合治疗患者中TCR克隆性的治疗变化，并将这些发现与免疫相关不良事件（irAE）发病的严重程度和时间联系起来。这些结果证明了与ICI诱导的毒性有关的循环T细胞特征，并对改善诊断和临床管理有意义。

据介绍，在接受ICI治疗的黑色素瘤患者中，有高达60%的患者发生严重的irAE。然而，目前还不知道在irAE发展之前是否有一个共同的基线免疫状态。

附：英文原文

Title: T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma

Author: Lozano, Alexander X., Chaudhuri, Aadel A., Nene, Aishwarya, Bacchiocchi, Antonietta, Earland, Noah, Vesely, Matthew D., Usmani, Abul, Turner, Brandon E., Steen, Chlo B., Luca, Bogdan A., Badri, Ti, Gulati, Gunsagar S., Vahid, Milad R., Khameneh, Farnaz, Harris, Peter K., Chen, David Y., Dhodapkar, Kavita, Sznol, Mario, Halaban, Ruth, Newman, Aaron M.

Issue&Volume: 2022-01-13

Abstract: Severe immune-related adverse events (irAEs) occur in up to 60% of patients with melanoma treated with immune checkpoint inhibitors (ICIs). However, it is unknown whether a common baseline immunological state precedes irAE development. Here we applied mass cytometry by time of flight, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing and bulk T cell receptor (TCR) sequencing to study peripheral blood samples from patients with melanoma treated with anti-PD-1 monotherapy or anti-PD-1 and anti-CTLA-4 combination ICIs. By analyzing 93 pre- and early on-ICI blood samples and 3 patient cohorts (n=27, 26 and 18), we found that 2 pretreatment factors in circulation—activated CD4 memory T cell abundance and TCR diversity—are associated with severe irAE development regardless of organ system involvement. We also explored on-treatment changes in TCR clonality among patients receiving combination therapy and linked our findings to the severity and timing of irAE onset. These results demonstrate circulating T cell characteristics associated with ICI-induced toxicity, with implications for improved diagnostics and clinical management.

DOI: 10.1038/s41591-021-01623-z

Source: https://www.nature.com/articles/s41591-021-01623-z