title: Intact interferon signaling in peripheral blood leukocytes of high-grade osteosarcoma patients.
abstract: High-grade osteosarcoma has a poor prognosis with an overall survival rate of about 60 percent. The recently closed European and American Osteosarcoma Study Group (EURAMOS)-1 trial investigates the efficacy of adjuvant chemotherapy with or without interferon-α. It is however unknown whether the interferon-signaling pathways in immune cells of osteosarcoma patients are functional. We studied the molecular and functional effects of interferon treatment on peripheral blood lymphocytes and monocytes of osteosarcoma patients, both in vivo and ex vivo. In contrast to other tumor types, in osteosarcoma, interferon signaling as determined by the phosphorylation of signal transducer and activator of transcription (STAT)1 at residue 701 was intact in immune cell subsets of 33 osteosarcoma patients as compared to 19 healthy controls. Also, cytolytic activity of interferon-α stimulated natural killer cells against allogeneic (n = 7 patients) and autologous target cells (n = 3 patients) was not impaired. Longitudinal monitoring of three osteosarcoma patients on interferon-α monotherapy revealed a relative increase in the CD16-positive subpopulation of monocytes during treatment. Since interferon signaling is intact in immune cells of osteosarcoma patients, there is a potential for indirect immunological effects of interferon-α treatment in osteosarcoma.
authors.affiliation: Department of Pediatrics,Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Emilie P
authors.initials: EP
authors.lastname: Buddingh
authors.forename: S Eriaty N
authors.initials: SE
authors.lastname: Ruslan
authors.forename: Dagmar
authors.initials: D
authors.lastname: Berghuis
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.forename: Jakob K
authors.initials: JK
authors.lastname: Anninga
authors.forename: Pancras C W
authors.initials: PC
authors.lastname: Hogendoorn
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schilham
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000188:drug therapy / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use; D020014:K562 Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D016898:Interferon-alpha; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human