title: Dexamethasone mediated inhibition of local IL-2 immunotherapy is dose dependent in experimental brain tumors.
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.
authors.affiliation: Division of Neurosurgery, The University of Chicago Hospitals, Chicago, IL 60637, USA. mlesniak@surgery.bsd.uchicago.edu
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
authors.forename: Patrick
authors.initials: P
authors.lastname: Gabikian
authors.forename: Betty M
authors.initials: BM
authors.lastname: Tyler
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Henry
authors.initials: H
authors.lastname: Brem
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: D005938:Glucocorticoids; D007376:Interleukin-2; D003907:Dexamethasone