Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination.
Immunization with dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL), which is responsible for tumor protection and regression. In this study, we examined whether DCs pulsed with necrotic tumor lysates can efficiently prevent malignant melanoma tumor cell metastasis to the lung. DCs derived from mouse bone marrow were found to produce remarkably elevated levels of IL-12 after being pulsed with the tumor lysates. Moreover, immunization with these DCs induced CTL activation and protected mice from metastasis development by intravenously inoculated tumor cells. In addition, these DCs activated NK cells in vitro in a contact-dependent manner, and induced NK activities in vivo. Furthermore, NK cell depletion before DC vaccination significantly reduced the tumor-specific CTL activity, IFN-gamma production, and IFN-gamma- inducible gene expression, and eventually interfered with the antitumor effect of tumor-pulsed DCs. Finally, similar findings with respect to NK cell dependency were obtained in the C57BL/ 6J-bg/bg mice, which have severe deficiency in cytolytic activity of NK cells. These data suggest that the antitumor effect elicited by DC vaccination, at least in a B16 melanoma model, requires the participation of both cytolytic NK and CD8(+) T cells. The findings of this study would provide important data for the effective design of DC vaccines for cancer immunotherapy.
Kim
Aeyung
A
Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-600, Korea.
Noh
Young-Woock
YW
Kim
Kwang Dong
KD
Jang
Yong-Suk
YS
Choe
Yong-Kyung
YK
Lim
Jong-Seok
JS
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D054410:Chemokine CCL7; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019496:Cancer Vaccines; C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma