帕克利塔塞尔驱动TREM2+巨细胞扩张,与Nab-paclitaxel相比,其治疗疗效较低
Yuqi Xing1,2,3, Ruiqi Zhong4,5, Qianchen Li1,2,3
1School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Nature communications
|February 2, 2026
概括
帕克利塔塞尔,而不是纳布-帕克利塔塞尔,增加TREM2+巨细胞,促进乳腺癌的肺转移. 向TREM2可能会改善帕克利塔塞尔的疗效,并减少转移.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 帕克利塔塞尔和纳布-帕克利塔塞尔表现出不同的临床疗效和免疫微环境影响.
- 这些差异背后的分子机制尚未完全理解.
研究的目的:
- 调查帕克利塔塞尔和纳布-帕克利塔塞尔对乳腺癌进展和瘤免疫微环境的差异性影响.
- 阐明TREM2 (在骨髓细胞2上表达的触发受体) 和相关巨细胞在帕克利塔塞尔诱导的转移中的作用.
主要方法:
- 对患者数据的元分析.
- 在体内研究使用母性小鼠模型的乳腺癌.
- 包括基因表达和细胞因子轴研究在内的分子分析.
- 基因切除和TREM2的反意义寡核酸向.
主要成果:
- 在女性乳腺癌患者中,nab-paclitaxel的响应率高于paclitaxel.
- 帕克利塔塞尔与纳布-帕克利塔塞尔不同,在与瘤相关的巨细胞中增加了TREM2表达.
- 帕克利塔塞尔通过ATF3-FGF2和EGR1-TREM2-EMT轴通过TREM2+巨细胞的招募促进了小鼠的肺转移.
- 抑制TREM2抑制了帕克利塔塞尔驱动的转移.
结论:
- 帕克利塔塞尔,但不是纳布-帕克利塔塞尔,刺激TREM2表达并扩大TREM2+巨细胞.
- 这种扩张有助于帕克利塔塞尔诱导的乳腺癌肺转移.
- 向TREM2是一个潜在的策略,可以增强帕克利塔塞尔治疗并减轻其转移潜力.
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