title: Copy number loss of the interferon gene cluster in melanomas is linked to reduced T cell infiltrate and poor patient prognosis.
abstract: 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.
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, Seattle, WA, United States of America.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Linsley
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, Seattle, WA, United States of America.
authors.forename: Cate
authors.initials: C
authors.lastname: Speake
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, Seattle, WA, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Whalen
authors.affiliation: Department of Systems Immunology, Benaroya Research Institute, Seattle, WA, United States of America.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
mesh_terms: D056915:DNA Copy Number Variations; D005260:Female; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D005810:Multigene Family; D011379:Prognosis; D016016:Proportional Hazards Models; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007370:Interferon Type I