在早期三阴性乳腺癌中接受新辅助化疗加杜尔瓦卢马布后的周围血液免疫参数,反应和不良事件
Julia Foldi1,2,3, Kim R M Blenman4,5,6, Michal Marczyk4,7
1Department of Internal Medicine, Section of Medical Oncology, Yale University, New Haven, CT, USA. Foldij@upmc.edu.
Breast cancer research and treatment
|July 13, 2024
概括
在接受化疗加杜瓦卢马布的三阴性乳腺癌 (TNBC) 患者的免疫细胞受体多样性和细胞因子水平没有预测治疗反应. 然而,基线细胞因子可以预测与免疫相关的不良事件 (irAEs).
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 基因组学就是基因组学.
背景情况:
- 三阴性乳腺癌 (TNBC) 是一种具有有限向治疗的侵袭性亚型.
- 新辅助化疗与杜尔瓦卢马布等免疫检查点抑制剂相结合,在TNBC治疗中显示出有前途.
- 了解免疫反应和生物标志物对于预测治疗结果和不良事件至关重要.
研究的目的:
- 评估T细胞受体 (TCR) 和B细胞受体 (BCR) 在TNBC患者的谱系多样性.
- 评估新辅助化疗加上杜尔瓦卢马布前后的血清细胞因子概况.
- 确定免疫标记物,病理反应和免疫相关不良事件 (irAEs) 之间的关联.
主要方法:
- 在66名TNBC患者的外周血液样本上使用Immunoseq平台分析了TCR和BCR谱的多样性.
- 使用Pielou的均度指数量化多样性,并通过MILLIPLEX MAP测定测量了38种血清细胞因子.
- 免疫标志物水平的比较以及具有和没有病理完整反应 (pCR) 和irAEs的组之间的多样性.
主要成果:
- 观察到高TCR和BCR多样性,但基线或多样性变化与病理反应或irAEs无关.
- 在治疗后,在患有irrAEs (p=0.0321) 的患者中,BCR多样性显著下降.
- 特定细胞因子 (IFNγ,IL-7,GM-CSF) 在患有irAEs的患者治疗前升高,而IL-8水平根据反应而有所不同.
结论:
- 基线血清细胞因子水平可以作为TNBC患者治疗免疫疗法和化疗的irAEs的预测生物标志物.
- 治疗后的B细胞克隆扩张可能在调解irAEs方面发挥作用.
- 需要进一步的研究来验证这些发现,并探索针对免疫反应的治疗策略.
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