瘤对缺氧的反应:了解缺氧瘤的微环境,以改善固体瘤的治疗结果
Kamilla Ja Bigos1, Conrado G Quiles1, Sapna Lunj1
1Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom.
Frontiers in oncology
|February 14, 2024
概括
固体瘤中的缺氧激活缺氧诱导因子 (HIF),驱动瘤生长和治疗阻力. 了解瘤微环境 (TME) 的复杂性对于开发有效的缺氧生物标志物和疗法至关重要.
科学领域:
- 在瘤学瘤学.
- 瘤微环境研究 研究
- 癌症生物学 癌症生物学
背景情况:
- 缺氧在固体瘤中普遍存在,显著影响瘤生物学和治疗反应.
- 缺氧诱导因子 (HIF) 通过缺氧激活驱动关键的瘤发生过程,如血管生成,免疫逃避和代谢重编程.
- 瘤微环境 (TME),包括细胞外基质 (ECM) 和细胞组件,在缺氧介导的治疗耐药性中发挥着关键作用.
研究的目的:
- 审查瘤缺氧对TME的多方面的影响.
- 探索ECM组件和癌症相关纤维细胞 (CAFs) 在缺氧驱动的瘤进展和治疗抵抗中的作用.
- 讨论缺氧生物标志物和临床环境中的向治疗的潜力和挑战.
主要方法:
- 文献综述综合了有关缺氧,HIF,TME组件 (ECM,CAF,免疫细胞) 和它们的相互作用的当前知识.
- 对矩阵刚度,CAF亚型和在低氧条件下免疫细胞调节的现有数据的分析.
- 检查对治疗耐药性的影响和开发新型治疗策略.
主要成果:
- 缺氧诱导的HIF激活促进瘤生长,血管生成,免疫逃避和代谢重编程,有助于治疗耐药性.
- ECM,特别是其由酸氧化酶 (LOX) 等酶调节的刚性,以及CAFs的多样性作用显著影响瘤行为和治疗结果.
- 缺氧调节免疫细胞,影响PD-L1等免疫疗法的疗效,并且可以对传统疗法产生抗性.
结论:
- 对缺氧TME的全面理解对于开发有效的癌症治疗是必不可少的.
- 开发临床适用的缺氧检测方法和向治疗仍然是一个重大挑战.
- 需要对CAF异质性和ECM动态进行进一步的研究,以充分阐明它们的作用并利用它们的治疗益处.
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