IMMUNE NETWORK
- Volume 3 Issue 3
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- Pages.188-200
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- 2003
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- 1598-2629(pISSN)
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- 2092-6685(eISSN)
IL-12 Production and Subsequent Natural Killer Cell Activation by Necrotic Tumor Cell-loaded Dendritic Cells in Therapeutic Vaccinations
- Kim, Aeyung (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
- Kim, Kwang Dong (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
- Choi, Seung-Chul (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
- Jeong, Moon-Jin (Department of Oral Histology, College of Dentistry, Chosun University) ;
- Lee, Hee Gu (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
- Choe, Yong-Kyung (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology) ;
- Paik, Sang-Gi (Department of Biology, Chungnam National University) ;
- Lim, Jong-Seok (Laboratory of Cell Biology, Korea Research Institute of Bioscience and Biotechnology)
- Published : 2003.09.30
Abstract
Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-