title: Gene expression profiling reveals similarities between the in vitro and in vivo responses of immune effector cells to IFN-alpha.
abstract: OBJECTIVE
  The precise molecular targets of IFN-alpha therapy in the context of malignant melanoma are unknown but seem to involve signal transducers and activators of transcription 1 signal transduction within host immune effector cells. We hypothesized that the in vitro transcriptional response of patient peripheral blood mononuclear cells (PBMC) to IFN-alpha would be similar to the in vivo response to treatment with high-dose IFN-alpha.
  
  
  METHODS
  The gene expression profiles of PBMCs and immune cell subsets treated in vitro with IFN-alpha were evaluated, as were PBMCs obtained from melanoma patients receiving adjuvant IFN-alpha.
  
  
  RESULTS
  Twenty-seven genes were up-regulated in PBMCs from normal donors after treatment with IFN-alpha in vitro for 18 hours (>2-fold, P < 0.001). A subset of these genes (in addition to others) was significantly expressed in IFN-alpha-treated T cells, natural killer cells, and monocytes. Analysis of gene expression within PBMCs from melanoma patients (n = 13) receiving high-dose IFN-alpha-2b (20 MU/m(2) i.v.) revealed significant up-regulation (>2-fold) of 21 genes (P < 0.001). Also, the gene expression profile of in vitro IFN-alpha-stimulated patient PBMCs was similar to that of PBMCs obtained from the same patient after IFN-alpha therapy.
  
  
  CONCLUSIONS
  This report is the first to describe the transcriptional response of T cells, natural killer cells, and monocytes to IFN-alpha and characterize the transcriptional profiles of PBMCs from melanoma patients undergoing IFN-alpha immunotherapy. In addition, it was determined that microarray analysis of patient PBMCs after in vitro stimulation with IFN-alpha may be a useful predictor of the in vivo response of immune cells to IFN-alpha immunotherapy.
authors.affiliation: Integrated Biological Sciences Graduate Program, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Zimmerer
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Lesinski
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.forename: Michael D
authors.initials: MD
authors.lastname: Radmacher
authors.forename: Carl
authors.initials: C
authors.lastname: Noble
authors.forename: Kari
authors.initials: K
authors.lastname: Kendra
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Walker
authors.forename: William E
authors.initials: WE
authors.lastname: Carson
mesh_terms: D001782:Blood Donors; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D046228:Microarray Analysis; D009000:Monocytes / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins
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