系统分析揭示了 ER 乳腺癌患者血液中反复失调的细胞因子信号传导反应。
Systems profiling reveals recurrently dysregulated cytokine signaling responses in ER+ breast cancer patients' blood.
发表日期：2024 Oct 10
作者：
Brian Orcutt-Jahns, Joao Rodrigues Lima Junior, Emily Lin, Russell C Rockne, Adina Matache, Sergio Branciamore, Ethan Hung, Andrei S Rodin, Peter P Lee, Aaron S Meyer
来源：
npj Systems Biology and Applications
摘要：
细胞因子协同作用以维持免疫稳态并协调免疫反应。在 ER 乳腺癌病例中，外周免疫细胞对多种细胞因子的反应发生改变，这些改变与患者的预后密切相关。为了从系统层面理解这种失调，我们测量了健康对照组和 ER 乳腺癌患者外周血中免疫细胞类型的一组细胞因子反应和受体丰度。使用张量分解对这种多维数据进行建模，我们发现乳腺癌患者表现出广泛的反应变化，包括对 IL-10 的反应急剧降低以及 pSmad2/3 和 pSTAT4 的基础水平升高。 ER 患者的 PD-L1、IL6Rα 和 IL2Rα 等受体也上调。尽管如此，对细胞因子反应的改变并不能用受体丰度的变化来解释。因此，张量分解有助于揭示免疫系统的协调重编程，这在我们的队列中是一致的。© 2024。作者。
Cytokines operate in concert to maintain immune homeostasis and coordinate immune responses. In cases of ER+ breast cancer, peripheral immune cells exhibit altered responses to several cytokines, and these alterations are correlated strongly with patient outcomes. To develop a systems-level understanding of this dysregulation, we measured a panel of cytokine responses and receptor abundances in the peripheral blood of healthy controls and ER+ breast cancer patients across immune cell types. Using tensor factorization to model this multidimensional data, we found that breast cancer patients exhibited widespread alterations in response, including drastically reduced response to IL-10 and heightened basal levels of pSmad2/3 and pSTAT4. ER+ patients also featured upregulation of PD-L1, IL6Rα, and IL2Rα, among other receptors. Despite this, alterations in response to cytokines were not explained by changes in receptor abundances. Thus, tensor factorization helped to reveal a coordinated reprogramming of the immune system that was consistent across our cohort.© 2024. The Author(s).