Intact interferon signaling in peripheral blood leukocytes of high-grade osteosarcoma patients

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• 作者：Emilie P. Buddingh (1)
  S. Eriaty N. Ruslan (1)
  Dagmar Berghuis (12)
  Hans Gelderblom (3)
  Jakob K. Anninga (1)
  Pancras C. W. Hogendoorn (2)
  R. Maarten Egeler (1)
  Marco W. Schilham (1)
  Arjan C. Lankester (1) A.Lankester@lumc.nl
• 关键词：Osteosarcoma – ; Tumor immunology – ; Interferon ; &#945 ; – ; NK cell
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：61
• 期：6
• 页码：941-947
• 全文大小：456.1 KB
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• 作者单位：1. Department of Pediatrics, J6-S, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands2. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands3. Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

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.