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-γ- 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.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Kim, A., Noh, YW., Kim, K. et al. Activated natural killer cell-mediated immunity is required for the inhibition of tumor metastasis by dendritic cell vaccination. Exp Mol Med 36, 428–443 (2004). https://doi.org/10.1038/emm.2004.55
Published:
Issue Date:
DOI: https://doi.org/10.1038/emm.2004.55
Keywords
This article is cited by
-
Recombinant Vesicular Stomatitis Virus Transduction of Dendritic Cells Enhances Their Ability to Prime Innate and Adaptive Antitumor Immunity
Molecular Therapy (2009)
-
Inhibition of lung metastasis in mice by intravascular injection of dendritic cells and natural killer cells
Biotechnology Letters (2009)
-
Synergy of adoptive T-cell therapy and intratumoral suicide gene therapy is mediated by host NK cells
Gene Therapy (2007)
-
NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity
Cancer Immunology, Immunotherapy (2006)