Orcutt-Jahns Brian, Junior Joao Rodrigues Lima, Rockne Russell C, Matache Adina, Branciamore Sergio, Hung Ethan, Rodin Andrei S, Lee Peter P, Meyer Aaron S
Department of Bioengineering, University of California, Los Angeles (UCLA), USA.
Department of Immuno-Oncology, Beckman Research Institute of the City of Hope, Duarte, CA, USA.
bioRxiv. 2023 Nov 3:2023.10.31.564987. doi: 10.1101/2023.10.31.564987.
Cytokines mediate cell-to-cell communication across the immune system and therefore are critical to immunosurveillance in cancer and other diseases. Several cytokines show dysregulated abundance or signaling responses in breast cancer, associated with the disease and differences in survival and progression. Cytokines operate in a coordinated manner to affect immune surveillance and regulate one another, necessitating a systems approach for a complete picture of this dysregulation. Here, we profiled cytokine signaling responses of peripheral immune cells from breast cancer patients as compared to healthy controls in a multidimensional manner across ligands, cell populations, and responsive pathways. We find alterations in cytokine responsiveness across pathways and cell types that are best defined by integrated signatures across dimensions. Alterations in the abundance of a cytokine's cognate receptor do not explain differences in responsiveness. Rather, alterations in baseline signaling and receptor abundance suggesting immune cell reprogramming are associated with altered responses. These integrated features suggest a global reprogramming of immune cell communication in breast cancer.
细胞因子介导免疫系统中细胞间的通讯，因此对癌症及其他疾病的免疫监视至关重要。几种细胞因子在乳腺癌中显示出丰度失调或信号反应异常，这与疾病以及生存和进展差异相关。细胞因子以协调的方式发挥作用，影响免疫监视并相互调节，因此需要采用系统方法来全面了解这种失调情况。在这里，我们以多维方式，对比健康对照，分析了乳腺癌患者外周免疫细胞在配体、细胞群体和反应途径方面的细胞因子信号反应。我们发现，细胞因子反应性在不同途径和细胞类型中的改变，通过跨维度的综合特征能得到最佳定义。细胞因子同源受体丰度的改变并不能解释反应性的差异。相反，提示免疫细胞重编程的基线信号和受体丰度的改变与反应改变相关。这些综合特征表明乳腺癌中免疫细胞通讯存在整体重编程。
