B7-1 expression decreases tumorigenicity and induces partial systemic immunity to murine neuroblastoma deficient in major histocompatibility complex and costimulatory molecules.
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.
Katsanis
E
E
Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
Xu
Z
Z
Bausero
M A
MA
Dancisak
B B
BB
Gorden
K B
KB
Davis
G
G
Gray
G S
GS
Orchard
P J
PJ
Blazar
B R
BR
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
D000911:Antibodies, Monoclonal; D018122:B7-1 Antigen; D006183:H-2 Antigens; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1