Copy number loss of the interferon gene cluster in melanomas is linked to reduced T cell infiltrate and poor patient prognosis.
Copy number loss of the interferon gene cluster in melanomas is linked to reduced T cell infiltrate and poor patient prognosis.
复制标题
DOI：
10.1371/journal.pone.0109760
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chaussabel D
中科院分区：
文献类型：
--
作者：
Linsley PS;Speake C;Whalen E;Chaussabel D
虽然免疫疗法正在迅速成为癌症治疗的支柱，但我们对如何单独或联合最佳靶向它们的理解仍存在重大差距。在这里，我们描述了一种新的方法来监测水平的免疫细胞和途径的表达数据，从实体瘤使用预定义的组或模块的共调节免疫基因。我们发现，在诊断时，黑色素瘤中I型干扰素刺激基因（ISGs）的相互关联的子网络的表达显著预测患者的生存率，在较小程度上，辅助性T细胞/T细胞调节和NK/T细胞毒性细胞基因的子网络也是如此。作为一个组，具有降低的ISG和免疫基因水平的预后不良的肿瘤表现出位于染色体9p21.3的干扰素基因簇的显著拷贝数丢失。我们的研究证明了黑色素瘤中I型干扰素作用和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是最有益的。
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.
登录
查看更多内容
影响因子：
7.4
作者：
Hamid O;Schmidt H;Nissan A;Ridolfi L;Aamdal S;Hansson J;Guida M;Hyams DM;Gómez H;Bastholt L;Chasalow SD;Berman D
通讯作者：
Berman D
影响因子：
30.5
作者：
Dunn, GP;Bruce, AT;Schreiber, RD
通讯作者：
Schreiber, RD
DOI：
10.1198/106186006x133933
发表时间：
2006-09-01
影响因子：
2.4
作者：
Hothorn, Torsten;Hornik, Kurt;Zeileis, Achim
通讯作者：
Zeileis, Achim
影响因子：
158.5
作者：
Gogas, H;Ioannovich, J;Kirkwood, JM
通讯作者：
Kirkwood, JM
影响因子：
30.8
作者：
Falchi, Mario;Bataille, Veronique;Hayward, Nicholas K.;Duffy, David L.;Bishop, Julia A. Newton;Pastinen, Tomi;Cervino, Alessandra;Zhao, Zhen Z.;Deloukas, Panos;Soranzo, Nicole;Elder, David E.;Barrett, Jennifer H.;Martin, Nicholas G.;Bishop, D. Timothy;Montgomery, Grant W.;Spector, Timothy D.
通讯作者：
Spector, Timothy D.