Induction of natural killer cell-dependent antitumor immunity by the Autographa californica multiple nuclear polyhedrosis virus.
Wild-type Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) infects a variety of mammalian cell types in vitro, but does not replicate in these cells. We investigated the effects of AcMNPV in the induction of the immune response and tumor metastasis in mice. After intravenous injection, AcMNPV was taken up by the liver and spleen, and preferentially infected dendritic cells (DCs) and B cells in the spleen; costimulatory molecules CD40, CD80, and CD86 were upregulated in the DCs. The hepatic mononuclear cells (MNCs) in these animals were highly cytotoxic to natural killer (NK)-sensitive YAC-1 and B16 melanoma cells, but not to NK-resistant EL4 cells. Intravenous injection of AcMNPV-induced NK cell proliferation in the liver and spleen, and enhanced antitumor immunity in mice with B16 liver metastases. Furthermore, such treatment increased the survival of C57BL/6, J alpha 281 (-/-), and interferon (IFN)-gamma (-/-) mice that were previously injected with B16 tumor cells. AcMNPV injection did not enhance the survival of NK cell-depleted mice. Moreover, one AcMNPV treatment effectively prolonged survival in a B16 liver metastasis model, and was equivalent to five treatments with recombinant interleukin-12 (IL-12) protein. These findings suggest that AcMNPV efficiently stimulates NK cell-mediated antitumor immunity.
Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba, Japan.
Masayuki
M
Kitajima
Takayuki
T
Abe
Naoko
N
Miyano-Kurosaki
Masaru
M
Taniguchi
Toshinori
T
Nakayama
Hiroshi
H
Takaku
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D007109:Immunity / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D017924:Nucleopolyhedroviruses / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000276:immunology / Q000473:pathology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D018664:Interleukin-12; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase