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.
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Lesniak, M.S., Gabikian, P., Tyler, B.M. et al. Dexamethasone Mediated Inhibition of Local IL-2 Immunotherapy is Dose Dependent in Experimental Brain Tumors. J Neurooncol 70, 23–28 (2004). https://doi.org/10.1023/B:NEON.0000040821.50347.c5
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DOI: https://doi.org/10.1023/B:NEON.0000040821.50347.c5