DC therapy induces long-term NK reactivity to tumors via host DC.
We vaccinated mice with DC loaded with or without invariant NKT-cell ligand alpha-galactosylceramide and evaluated long-term resistance against tumor challenge. When mice had been given either DC or DC/galactosylceramide and were challenged with tumor cells even 6-12 months later, both NK and NKT cells were quickly activated to express CD69 and produce IFN-gamma. The NK cells could resist a challenge with several different tumors in vivo. The activated NK and NKT cells could be depleted with anti-NK1.1 treatment. In spite of this, the activated cells recovered, indicating that tumor-responsive NK and NKT cells were being generated continuously as a result of vaccination with DC and were not true memory cells. The NK and NKT antitumor response in DC-vaccinated mice depended on CD4(+) T cells, but neither CD8(+)T cells nor CD4(+)CD25(+) regulatory T cells. However, both vaccine DC and host DC were required for the development of long-term, tumor reactive innate immunity. These results indicate that DC therapy in mice induces long-lasting innate NK- and NKT-cell activation through a pathway that requires host DC and CD4(+) T cells and that the continued generation of active NK cells resists the establishment of metastases in vivo.
Shimizu
Kanako
K
Research Unit for Cellular Immunotherapy, The Institute of Physical and Chemical Research, RIKEN, Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Fujii
Shin-ichiro
S
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D007371:Interferon-gamma