Melanoma NOS1 expression promotes dysfunctional IFN signaling. Academic Article uri icon

Overview

abstract

  • In multiple forms of cancer, constitutive activation of type I IFN signaling is a critical consequence of immune surveillance against cancer; however, PBMCs isolated from cancer patients exhibit depressed STAT1 phosphorylation in response to IFN-α, suggesting IFN signaling dysfunction. Here, we demonstrated in a coculture system that melanoma cells differentially impairs the IFN-α response in PBMCs and that the inhibitory potential of a particular melanoma cell correlates with NOS1 expression. Comparison of gene transcription and array comparative genomic hybridization (aCGH) between melanoma cells from different patients indicated that suppression of IFN-α signaling correlates with an amplification of the NOS1 locus within segment 12q22-24. Evaluation of NOS1 levels in melanomas and IFN responsiveness of purified PBMCs from patients indicated a negative correlation between NOS1 expression in melanomas and the responsiveness of PBMCs to IFN-α. Furthermore, in an explorative study, NOS1 expression in melanoma metastases was negatively associated with patient response to adoptive T cell therapy. This study provides a link between cancer cell phenotype and IFN signal dysfunction in circulating immune cells.

publication date

  • April 1, 2014

Research

keywords

  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Interferon-alpha
  • Melanoma
  • Neoplasm Proteins
  • Nitric Oxide Synthase Type I
  • Signal Transduction

Identity

PubMed Central ID

  • PMC4001531

Scopus Document Identifier

  • 84899728545

Digital Object Identifier (DOI)

  • 10.1073/pnas.0913491107

PubMed ID

  • 24691438

Additional Document Info

volume

  • 124

issue

  • 5