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Acta Neuropathologica

, Volume 103, Issue 2, pp 171–178 | Cite as

Cytokine and cytokine receptor mRNA expression in human glioblastomas: evidence of Th1, Th2 and Th3 cytokine dysregulation

  • Chunhai Hao
  • Ian F. Parney
  • Wilson H. Roa
  • Joan Turner
  • Kenneth C. Petruk
  • David A. Ramsay
Regular Paper

Abstract.

Immunotherapies, although promising in preclinical studies, have not yet enhanced the survival of patients with glioblastomas. To further understand the immunobiology of glioblastomas in clinical settings, we examined 53 cytokine or cytokine receptor transcripts in 12 human glioblastomas and 6 human glioblastoma cell lines and correlated the findings with the degree of inflammation. Multi-probe RNase protection assays were used to examine Th1, Th2, and Th3 cytokine and cytokine receptor expression. Th2 [interleuking (IL)-6, leukemia inhibitory factor and oncostatin M] and Th3 (transforming growth factor-β1, 2, 3) cytokine and their receptor transcripts were strongly expressed in almost all glioblastomas and glioma cell lines. Two other Th2 cytokine receptor subunit transcripts (IL-4Rα and IL-13Rα) were also commonly detected. In contrast, although Th1 cytokine receptors tumor necrosis factor (TNF) RI, interferon (IFN)-γRα, IFN-γRβ, were detected, their cytokines (IFN-γ, TNF-α, lymphotoxin-α) were not. Transcripts for IL-2 family cytokine (IL-2, IL-7, IL-9, IL-15) and receptors (IL-2Rα, IL-2Rβ, γc, IL-7Rα, IL-9Rα, IL15Rα) and IL-12 family cytokine (IL-12p40) and receptors (IL-12Rβ1 and IL-12β2) were essentially absent in both tumors and cell lines. Immunohistochemical methods showed sparse T lymphocyte infiltrates and numerous microglia in the glioblastomas. This pattern indicates an 'immunosuppressive status' in glioblastomas and could account for the failure of immunotherapy in such tumors.

Cytokine Receptor Glioblastoma Cell lines Immunotherapy 

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Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Chunhai Hao
    • 1
  • Ian F. Parney
    • 2
  • Wilson H. Roa
    • 3
  • Joan Turner
    • 3
  • Kenneth C. Petruk
    • 2
  • David A. Ramsay
    • 4
  1. 1.Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
  2. 2.Department of Surgery, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
  3. 3.Department of Oncology, University of Alberta, Edmonton, Alberta, Canada T6G 2B7
  4. 4.Department of Pathology, University of Western Ontario, London, Ontario, Canada N6A 4G5

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