免疫微环境中的细胞相互作用是乳腺癌中抵抗细胞循环抑制的基础
Jason I Griffiths1,2, Patrick A Cosgrove3, Eric F Medina3
1Department of Medical Oncology & Therapeutics Research, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA. jasonigriff@gmail.com.
Nature communications
|March 3, 2025
概括
癌细胞通过改变瘤微环境,抑制免疫细胞来逃避CDK4/6抑制剂,如利博西基利布. 恢复免疫细胞通信可以提高ER+乳腺癌的治疗反应.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 癌细胞可以通过修改周围的瘤微环境 (TME) 来逃避治疗.
- 了解治疗期间的耐药性促进相互作用对于改善治疗疗效至关重要.
研究的目的:
- 研究瘤相关细胞的细胞组成,通信模式和表型,以应对内分泌疗法和CDK4/6抑制.
- 阐明在雌激素受体阳性 (ER+) 乳腺癌中对 ribociclib 的耐药性机制.
主要方法:
- 在II期和III期高风险ER+乳腺癌患者的连续瘤活检上进行单细胞RNA测序.
- 对瘤相关的髓状细胞和T细胞,细胞因子信号传递 (IL-15/18) 和体外共同培养实验的分析.
主要成果:
- 利博西克利布的耐药性涉及癌细胞的上调调节因子,这些因子促进免疫抑制性骨髓体分化,减少T细胞交叉通讯.
- 克服利博西基利布治疗的瘤表现出T细胞激活和招募的减少.
- 利博西克利布在体外抑制癌细胞生长和T细胞增殖/激活.
- 外源IL-15通过提高T细胞活性来增强CDK4/6抑制剂的有效性.
结论:
- 在ER+乳腺癌中,治疗反应取决于免疫细胞格局,它们的激活状态和细胞间通信网络.
- 针对TME内的免疫细胞相互作用,可以克服对CDK4/6抑制剂的抗性.
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