在质母细胞瘤中鉴定缺氧巨细胞,这些巨细胞在血管正常化方面具有治疗潜力
Wenying Wang1, Tianran Li1, Yue Cheng1
1Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Amy Medical University), and The Key Laboratory of Tumor Immunopathology, The Ministry of Education of China, Chongqing 400038, P.R. China.
Cancer cell
|April 19, 2024
概括
扩散性质瘤中的瘤透性巨细胞表现出不同的亚型. 向缺氧激活巨细胞 (缺氧-TAMs) 和它们的上腺素信号传递可以使瘤血管正常化并增强抗癌药物输送.
科学领域:
- 神经瘤学神经瘤学
- 瘤免疫学 瘤免疫学
- 癌症生物学 癌症生物学
背景情况:
- 单细胞衍生瘤关联巨细胞 (Mo-TAMs) 是扩散性质瘤中瘤微环境的关键组成部分.
- 这些巨细胞表现出显著的异质性和空间分布,影响瘤的进展和治疗反应.
研究的目的:
- 在扩散性结质瘤中描述Mo-TAMs的转录景观和空间分布.
- 为了研究一个特定的Mo-TAM子集在临死中的作用及其对瘤血管结构的影响.
- 探索针对Mo-TAM的治疗策略,以改善质母细胞瘤治疗.
主要方法:
- 单细胞转录组学应用于来自51名IDH野生型质母细胞瘤或IDH突变质母细胞瘤患者的Mo-TAM.
- 空间转录组学用于识别特定利基的Mo-TAM子集.
- 活体质母细胞瘤异种移植模型,以评估低氧-TAMs的功能和向上腺素信号的有效性.
主要成果:
- 一个不同的Mo-TAM子集,称为Hypoxia-TAM,在临死中被确定,其特征是缺氧反应的特征.
- 低氧-TAMs通过激活上腺素信号传递,破坏内皮附着结的稳定,促进瘤的超透性.
- 在体内阻断上腺素信号传递恢复了血管完整性,增强了内药物递送,并改善了治疗结果.
- 增加的缺氧-TAM比例或上腺素表达与瘤血管的透性和质母细胞瘤预后不佳相关.
结论:
- 在扩散性质瘤中,Mo-TAMs表现出显著的多样性和空间利基驱动的重编程.
- 低氧-TAMs在通过上腺素信号传递促进瘤血管超透性方面发挥着至关重要的作用.
- 向缺氧-TAM衍生的上腺素是一种有前途的治疗策略,可以使瘤血管正常化,并提高质母细胞瘤治疗的疗效.
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