Exp Mol Med.  2004 Oct;36(5):428-443.

Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination

• Kim A
• Noh YW
• Kim KD
• Jang YS
• Choe YK
• Lim JS

Abstract

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-g 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.

Keyword

cancer vaccines; cytotoxic T lymphocytes; dendritic cells; melanoma; natural killer cells

MeSH Terms

Animals
Antigen Presentation/immunology
CD8-Positive T-Lymphocytes/immunology
Cancer Vaccines/*therapeutic use
Cell Line, Tumor
Cytokines/biosynthesis/immunology
Dendritic Cells/immunology/*transplantation
Female
Interferon Type II/biosynthesis/immunology
Interleukin-12/biosynthesis/immunology
Killer Cells, Natural/*immunology
Lung Neoplasms/immunology/prevention & control/secondary
Lymphocyte Activation/immunology
Lymphocyte Depletion
Melanoma, Experimental/immunology/secondary/*therapy
Mice
Mice, Inbred C57BL
Monocyte Chemoattractant Proteins/biosynthesis/immunology
Research Support, Non-U.S. Gov't
T-Lymphocytes, Cytotoxic/immunology