Linsley Peter S, Speake Cate, Whalen Elizabeth, Chaussabel Damien
Department of Systems Immunology, Benaroya Research Institute, Seattle, WA, United States of America.
PLoS One. 2014 Oct 14;9(10):e109760. doi: 10.1371/journal.pone.0109760. eCollection 2014.
While immunotherapies are rapidly becoming mainstays of cancer treatment, significant gaps remain in our understanding of how to optimally target them, alone or in combination. Here we describe a novel method to monitor levels of immune cells and pathways in expression data from solid tumors using pre-defined groups or modules of co-regulated immune genes. We show that expression of an interconnected sub-network of type I interferon-stimulated genes (ISGs) in melanomas at the time of diagnosis significantly predicted patient survival, as did, to a lesser extent, sub-networks of T helper/T regulatory and NK/T Cytotoxic cell genes. As a group, poor prognosis tumors with reduced ISG and immune gene levels exhibited significant copy number loss of the interferon gene cluster located at chromosome 9p21.3. Our studies demonstrate a link between type I interferon action and immune cell levels in melanomas, and suggest that therapeutic approaches augmenting both activities may be most beneficial.
虽然免疫疗法正迅速成为癌症治疗的主要手段，但在如何单独或联合优化靶向免疫疗法方面，我们的认识仍存在重大差距。在此，我们描述了一种新方法，可利用预定义的共同调控免疫基因组或模块，监测实体瘤表达数据中的免疫细胞水平和信号通路。我们发现，黑色素瘤诊断时I型干扰素刺激基因（ISG）相互连接的子网络的表达显著预测了患者的生存率，T辅助/T调节细胞和NK/T细胞毒性细胞基因的子网络在较小程度上也有此作用。总体而言，ISG和免疫基因水平降低的预后不良肿瘤在位于9号染色体p21.3的干扰素基因簇上出现了显著的拷贝数缺失。我们的研究证明了黑色素瘤中I型干扰素作用与免疫细胞水平之间的联系，并表明增强这两种活性的治疗方法可能最有益。
