title: B7-1 expression decreases tumorigenicity and induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecules.
abstract: Neuroblastoma may escape an immune attack by virtue of its low expression of surface accessory molecules essential in the antitumor response. Murine neuroblastoma, neuro-2a, was transduced with the retroviral vector LB7-1SN to examine the influence of B7-1 expression on the immune response directed against a low major histocompatibility class (MHC) I and class II negative, B7-2, and ICAM-1 negative tumor. Using a retroperitoneal model for implantation of neuroblastoma in its natural site, we demonstrated that expression of B7-1 by neuro-2a reduces its tumorigenicity. Coinjection of B7-1-positive and -negative cells improved survival compared with mice receiving B7-1-negative cells alone. This was dependent on the ratio of B7-1+ to B7-1- neuro-2a cells injected. CD8+ and not CD4+ T-cell depletion significantly increased tumor-induced mortality in syngeneic A/J mice, indicating that B7-1 decreases tumorigenicity primarily by direct constimulation of CD8+ T cells. Rejection of N-2a/B7-1 tumors or preimmunization with irradiated N-2a/B7-1 cells die not increase protection to challenge with unmodified neuro-2a cells over mice vaccinated with N-2a/neo. Furthermore, cytotoxic T lymphocyte (CTL) precursor frequencies were not significantly higher after in vivo priming and in vitro stimulation with irradiated N-2a/B7-1 compared with N-2a/neo, indicating that B7-1 costimulation by the tumor, in the absence of adequate antigen presentation by MHC molecules, may limit the generation of effective CTLs.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
authors.forename: E
authors.initials: E
authors.lastname: Katsanis
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.forename: M A
authors.initials: MA
authors.lastname: Bausero
authors.forename: B B
authors.initials: BB
authors.lastname: Dancisak
authors.forename: K B
authors.initials: KB
authors.lastname: Gorden
authors.forename: G
authors.initials: G
authors.lastname: Davis
authors.forename: G S
authors.initials: GS
authors.lastname: Gray
authors.forename: P J
authors.initials: PJ
authors.lastname: Orchard
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology / Q000502:physiology / Q000627:therapeutic use; D005260:Female; D005822:Genetic Vectors; D006183:H-2 Antigens / Q000276:immunology*; D007114:Immunization; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D009368:Neoplasm Transplantation / Q000276:immunology; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use; D012186:Retroperitoneal Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D006183:H-2 Antigens; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1