1.Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine.
Jun Sik LEE ; Dae Hyun KIM ; Chang Min LEE ; Tae Kwun HA ; Kyung Tae NOH ; Jin Wook PARK ; Deok Rim HEO ; Kwang Hee SON ; In Duk JUNG ; Eun Kyung LEE ; Yong Kyoo SHIN ; Soon Cheol AHN ; Yeong Min PARK
Immune Network 2011;11(1):79-94
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-kappaB. 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-gamma 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.
Animals
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Dendritic Cells
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Immunotherapy
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Interleukin-12
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Lymph Nodes
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Lymphocyte Culture Test, Mixed
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Lymphocytes
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Mice
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Phenotype
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Podophyllotoxin
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T-Lymphocytes
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Toll-Like Receptors
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Up-Regulation
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Vaccination
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Vaccines