由骨髓细胞分泌的IL-23驱动了抵抗割的前列腺癌
Arianna Calcinotto1, Clarissa Spataro1, Elena Zagato1
1Institute of Oncology Research (IOR), Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Nature
|June 29, 2018
概括
骨髓衍生抑制细胞 (MDSC) 通过产生IL-23驱动抵抗割的前列腺癌 (CRPC). 阻断IL-23可以恢复对雄激素缺乏治疗的敏感性,为CRPC提供新的治疗策略.
科学领域:
- 癌症学
- 免疫学
- 癌症生物学
背景情况:
- 前列腺癌通常会对抗雄激素剥夺疗法,发展为抵抗割的前列腺癌 (CRPC).
- 瘤微环境对癌症的进展和治疗耐药性起着至关重要的作用.
- 了解驱动CRPC的机制对于开发有效疗法至关重要.
研究的目的:
- 研究瘤微环境在抵抗割的前列腺癌发展中的作用.
- 确定促进CRPC的微环境产生的特定因素.
- 探索针对这些因素的潜在治疗策略.
主要方法:
- 分析CRPC患者和小鼠的瘤样本和血液.
- 由骨髓衍生抑制细胞 (MDSC) 生产的细胞因子的鉴定.
- 在CRPC小鼠模型中使用抗体介导IL-23的活化实验.
主要成果:
- 由MDSCs产生的IL-23被确定为CRPC的关键驱动因素.
- 激活前列腺瘤细胞中的雄激素受体通路,在雄激素缺乏下促进生存和增殖.
- 在CRPC患者中观察到MDSC透和IL-23水平的增加.
- 在小鼠中阻断IL-23恢复了对抗雄激素缺乏治疗的敏感性.
结论:
- 通过分泌IL-23,MDSC通过非细胞自主机制促进CRPC.
- 向IL-23是一种有前途的治疗策略,可以克服前列腺癌中MDSC介导的割耐药性.
- 阻断IL-23可能与标准前列腺癌疗法产生协同作用.
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