在MIBC中缺氧ECM和中性粒细胞具有免疫疗法耐药性
Fraser Child1, Sapna Lunj2, Julie Gough3
1Division of Cancer Sciences, University of Manchester, Manchester, UK. fraser.child@manchester.ac.uk.
Nature reviews. Urology
|October 14, 2025
概括
免疫检查点抑制剂在肌肉侵入性膀癌中表现出有限的反应. 向缺氧,细胞外基质和中性粒细胞可能会改善非响应者的疗效.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 癌症生物学 癌症生物学
背景情况:
- 针对PD1/PDL1的免疫检查点抑制剂 (ICI) 提高了固体瘤的存活率.
- 在肌肉侵入性膀癌 (MIBC) 中,ICI的临床反应有限 (20-30%).
- 缺氧和中性粒细胞透在MIBC中很常见,并且与免疫疗法耐药性有关.
研究的目的:
- 了解MIBC中ICI耐药性的机制.
- 为了确定患者分层的生物标志物.
- 探索向缺氧,ECM和中性粒细胞以克服ICI抵抗.
主要方法:
- 调查低氧相关的细胞外矩阵 (ECM) 改造.
- 在低氧条件下分析中性粒细胞的招募,偏振和激活.
- 检查ECM和中性粒细胞对T细胞介导免疫疗法的影响.
主要成果:
- 与缺氧相关的ECM重塑会影响中性粒细胞的两极化和功能.
- 这些机制改变了免疫细胞的行为,可能会产生ICI耐药性.
- 涉及ECM和中性粒细胞的特定途径与免疫疗法耐药性有关.
结论:
- 了解缺氧,ECM和中性粒细胞相互作用对于MIBC免疫疗法至关重要.
- 针对这些途径可以提高ICI在不响应MIBC患者的疗效.
- 旨在改善70-80%的ICI非响应者的持久反应.
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