在免疫检查点抑制剂相关的毒性中,定居巨编排的免疫和纤维细胞相互作用
Yanhong Ma1,2, Yang Chen2,3, Qinfan Yao2
1Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|August 14, 2025
概括
免疫检查点抑制剂 (ICI) 可以导致损伤 (ICI-AN). 这项研究揭示了居住性巨细胞驱动ICI-AN,确定CXCL9作为生物标志物和MMP12作为缓解损伤的治疗标.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 免疫检查点抑制剂 (ICI) 彻底改变了癌症治疗,但可能导致与免疫相关的不良事件,包括ICI相关的毒性 (ICI-AN).
- 目前尚不完全了解ICI-AN的潜在机制,这阻碍了诊断和治疗方面的进展.
- 了解ICI-AN病原体对于管理癌症治疗副作用至关重要.
研究的目的:
- 阐明驱动ICI相关毒性的细胞和分子机制.
- 为ICI-AN.确定潜在的诊断生物标志物和治疗点.
- 为了研究ICI-AN中居民巨细胞的作用.
主要方法:
- 图像质量细胞计,转录组学和小鼠模型的综合分析.
- 检查ICI-AN患者的脏活检.
- 在小鼠中利用抗PD-1治疗来模拟损伤.
主要成果:
- 在ICI-AN患者的活检显示,居住性巨细胞,纤维细胞和CD8+T细胞的增加,巨细胞表达了亲炎和亲纤维细胞标志物.
- 在小鼠中,抗PD-1疗法诱导损伤,其特征是免疫细胞透,管状损伤和纤维化.
- 削弱居民巨细胞通过减少CXCL9和MMP12表达来减少损伤和纤维化,而不会影响抗瘤功效.
结论:
- 居民巨细胞是ICI相关毒性的主要驱动因素.
- 尿液中的CXCL9水平可以作为ICI-AN的诊断生物标志物.
- 由居住巨细胞表达的MMP12是缓解ICI-AN的潜在治疗标.
- 这项研究提供了对ICI-AN病原体和治疗毒性策略的新见解.
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