癌症中胸膜微环境重塑 癌症尾症作为检查点抑制剂有效性和毒性的决定因素
Run-Kai Huang1,2, Yan-Fang Xing3, Xiang-Yuan Wu1,2
1Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Journal of cachexia, sarcopenia and muscle
|July 16, 2025
概括
癌症缓解症损害了胆小板功能,导致T细胞选择和自身抗体生产的改变. 这会影响癌症患者的免疫检查点抑制剂 (ICI) 疗效,影响治疗结果.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
背景情况:
- 免疫检查点将自身免疫和癌症联系起来.
- 胸腺缩与自身免疫性炎症有关.
- 癌症缓解症对胸膜内置的影响及其临床意义尚不清楚.
研究的目的:
- 调查癌症缓解症对胸腺内置的影响.
- 确定缓解症诱导的胸膜变化的临床意义.
- 探索与免疫检查点抑制剂 (ICI) 治疗疗效的相关性.
主要方法:
- 单细胞测序,免疫光和流动细胞测量在正型肝细胞癌 (HCC) 的小鼠中.
- 在 cachectic HCC 鼠标模型中对胸膜变化的分析.
- 对接受抗PD-1/L1抗体治疗的癌症患者进行后续研究,以将血清自身抗体与ICI疗效相关联.
主要成果:
- 在HCC小鼠中,甲状腺硬化导致甲状腺纤维细胞不成熟,抗原处理受损,与甲状腺细胞的相互作用减少.
- 卡切克性小鼠表现出甲状腺髓降解和纤维细胞基因表达的改变,这表明T细胞负选择受损.
- 癌症卡赫西克性红色素原生细胞诱导了原生细胞死亡和减少了特定的髓性纤维细胞;在卡赫西克性小鼠和ICI治疗患者中观察到较高的自身抗体,与治疗结果相关.
结论:
- 癌症缓解症扰乱了髓纤维细胞的成熟,损害了T细胞的负性选择,并扩大了T细胞受体谱对抗受组织限制的抗原.
- 这些缓解症诱导的胸膜变化可能会调解ICI在癌症治疗中的不利和有利影响.
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