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KMID : 0923620110110010079
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Immune Network
2011 Volume.11 No. 1 p.79 ~ p.94
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Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine
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Lee Jun-Sik
Kim Dae-Hyun
Lee Chang-Min
Ha Tae-Kwun
Noh Kyung-Tae
Park Jin-Wook
Heo Deok-Rim
Son Kwang-Hee
Jung In-Duk
Lee Eun-Kyung
Shin Yong-Kyoo
Ahn Soon-Cheol
Park Yeong-Min
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Abstract
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Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-?B.
Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma.
Results: DPT promoted the activation of CD8＋ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-? production and induction of cytotoxic T lymphocyte activity.
Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.
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KEYWORD
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Dendritic cells, Deoxypodophyllotoxin, Interleukin-12, CTL activity, DC-based vaccination
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