低HER2乳腺癌是免疫冷:洞察瘤透免疫细胞和对免疫治疗的影响
S Pizzamiglio1, A Blanda1, V Appierto2
1Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
NPJ breast cancer
|December 2, 2025
概括
在HER2阴性早期乳腺癌 (EBC) 中,HER2表达与免疫细胞透率降低相关,影响免疫疗法的有效性. 低HER2的EBC显示反应减弱,这表明针对HER2的治疗可能有利于这些患者.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 遗传学 遗传学 是一个
背景情况:
- HER2表达是乳腺癌的关键生物标志物,但其在HER2-阴性早期乳腺癌 (EBC) 中对免疫透和免疫治疗反应的作用尚未完全理解.
- 了解HER2-阴性EBC中的瘤免疫微环境对于优化治疗策略至关重要.
研究的目的:
- 为了研究HER2表达,免疫透和免疫治疗反应在HER2-阴性早期乳腺癌之间的关联.
- 为了确定不同的HER2表达水平 (HER2-0与HER2-low) 是否会影响免疫细胞丰度和免疫疗法的临床结果.
主要方法:
- 来自三个独立队列 (发现,确认,ABiM) 的基因表达数据的分析,以使用20个基因签名量化HER2表达.
- 使用CIBERSORTx.进行免疫细胞透的评估.
- 相关性和协同变异的分析被用来评估HER2表达,免疫细胞和免疫治疗反应之间的关联,在一个新辅助的现实世界队列.
主要成果:
- 增加的HER2表达始终与细胞毒性CD8+T细胞和M1巨细胞的透减少有关.
- HER2表达独立地预测了B细胞和血细胞的较低丰度.
- 在新辅助免疫疗法队列中,HER2-低瘤与HER2-0瘤相比,表现出较低的中期和病理完整响应率.
结论:
- HER2表达定义了HER2-阴性EBC中的"免疫感冒"表型,这与免疫治疗反应较差有关.
- 这些发现支持对HER2-低水平早期乳腺癌患者的HER2-向组合疗法的研究,以克服免疫抵抗.
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