Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccineopen access
- Authors
- 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
- Issue Date
- Feb-2011
- Publisher
- 대한면역학회
- Keywords
- Dendritic cells; Deoxypodophyllotoxin; Interleukin-12; CTL activity; DC-based vaccination
- Citation
- Immune Network, v.11, no.1, pp 79 - 94
- Pages
- 16
- Journal Title
- Immune Network
- Volume
- 11
- Number
- 1
- Start Page
- 79
- End Page
- 94
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/33863
- DOI
- 10.4110/in.2011.11.1.79
- ISSN
- 1598-2629
2092-6685
- Abstract
- 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-κB.
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-γproduction 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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