title: Immunological responsiveness to interleukin-2-producing brain tumors can be restored by concurrent subcutaneous transplantation of the same tumors.
abstract: The central nervous system shows tolerance for activated host immune reactions, and this relative unresponsiveness may lessen the efficacy of an immunotherapy for brain tumors. Using interleukin-2 (IL-2)-producing 9L rat gliosarcoma cells (9L/IL-2), we examined whether secretion of IL-2 from subcutaneous (s.c.) and/or intracerebral (i.c.) tumors can elicit augmented immunological responses to brain tumors. Syngeneic rats could reject 9L/IL-2 cells inoculated s.c., but developed 9L/IL-2 brain tumors by i.c. inoculation. The growth of i.c. 9L/IL-2 tumors was, however, significantly retarded compared with that of i.c. wild-type tumors. The growth of i.c. wild-type tumors was significantly suppressed when the rats concurrently received 9L/IL-2 cells s.c. Moreover, most of the rats that were inoculated i.c. with 9L/IL-2 cells did not develop brain tumors when concurrently injected s.c. with 9L/IL-2 cells. Immunohistochemical analysis on i.c. 9L/IL-2 tumors, when the rats were concurrently inoculated s.c. with 9L/IL-2 cells, revealed that migration of CD4+ or CD8+ T cells, monocytes/microglias, and macrophages was markedly augmented to a similar level as found in the s.c. 9L/IL-2 tumors. These results showed that systemic immune responses to brain tumor were induced in an immunologically privileged site by concurrent s.c. inoculation of the same tumors that produce IL-2. The present study may also raise the possibility of a therapeutic strategy for brain tumors by the combinatory expression of IL-2 gene using s.c. immunization followed by direct gene transfer into brain tumors.
authors.affiliation: Department of Neurosurgery, School of Medicine, Chiba University, Japan. iwadate@med.m.chiba-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Iwadate
authors.forename: M
authors.initials: M
authors.lastname: Tagawa
authors.forename: H
authors.initials: H
authors.lastname: Namba
authors.forename: M
authors.initials: M
authors.lastname: Oga
authors.forename: K
authors.initials: K
authors.lastname: Kawamura
authors.forename: K
authors.initials: K
authors.lastname: Tasaki
authors.forename: S
authors.initials: S
authors.lastname: Sakiyama
authors.forename: A
authors.initials: A
authors.lastname: Yamaura
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015316:Genetic Therapy; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology*; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; D007376:Interleukin-2; D004247:DNA