Copy number loss of the interferon gene cluster in melanomas is linked to reduced T cell infiltrate and poor patient prognosis

PLoS One. 2014 Oct 14;9(10):e109760. doi: 10.1371/journal.pone.0109760. eCollection 2014.

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.

MeSH terms

  • DNA Copy Number Variations
  • Female
  • Gene Expression
  • Humans
  • Interferon Type I / genetics*
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / genetics*
  • Melanoma / immunology
  • Melanoma / mortality
  • Middle Aged
  • Multigene Family
  • Prognosis
  • Proportional Hazards Models
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / mortality
  • T-Lymphocytes / immunology*

Substances

  • Interferon Type I

Grant support

The authors have no support or funding to report.