IL-12 production and subsequent natural killer cell activation by necrotic tumor cell-loaded dendritic cells in therapeutic vaccinations

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IL-12 production and subsequent natural killer cell activation by necrotic tumor cell-loaded dendritic cells in therapeutic vaccinations
Ae Yung Kim; Kwang Dong Kim; Seung-Chul Choi; M J Jeong; Hee Gu Lee; Yong Kyung Choe; S G Paik; Jong-Seok Lim
Bibliographic Citation
Immune Network, vol. 3, no. 3, pp. 188-200
Publication Year
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-γ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.
dendritic cells (DC)IL-12NK cellscytotoxic T lymphocytes (CTL)IFN-γ
Korea Soc-Assoc-Inst
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Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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