Dexamethasone mediated inhibition of local IL-2 immunotherapy is dose dependent in experimental brain tumors

Maciej S. Lesniak*, Patrick Gabikian, Betty M. Tyler, Drew M. Pardoll, Henry Brem

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Local delivery of cytokines has been shown to have a potent anti-tumor activity against a wide range of malignant brain tumors. In this study, we examined the role of systemic immunosuppression using dexamethasone on the efficacy of local IL-2 immunotherapy in treating experimental murine CNS tumors. An endothelial cell line secreting hIL-2 (NTC-121) was injected intracranially in C57BL/6 mice (n = 10/group) along with B16/F10 (wild type) melanoma cells. A separate set of animals also received daily injections of either 1 mg/k or 10 mg/kg of dexamethasone. Sixty percent of mice treated with IL-2 (P < 0.001 vs. control) vs. 55% (P < 0.005) of mice treated with IL-2 and 1 mg/kg of dexamethasone were long-term survivors (LTS) of >120 days. There was no difference in survival between control animals that received only wild type cells or animals that were treated with IL-2 and 10 mg/kg of dexamethasone. Histopathological examination of brains from animals sacrificed at different times showed an accumulation of CD8 + T-cells around the site of the injected tumor only in the IL-2 group and the group that received 1 mg/kg of dexamethasone. These results suggest that while high doses of dexamethasone can completely inhibit the immune response observed with IL-2, lower and more likely therapeutic doses of dexamethasone do not inhibit local IL-2 immunotherapy.

Original languageEnglish (US)
Pages (from-to)23-28
Number of pages6
JournalJournal of Neuro-Oncology
Volume70
Issue number1
DOIs
StatePublished - Oct 1 2004

Keywords

  • Brain tumors
  • Dexamethasone
  • Histopathology
  • Immunohistochemistry
  • Immunotherapy
  • Interleukins
  • Steroids

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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