title: Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine.
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-γ production and induction of cytotoxic T lymphocyte activity.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, College of Natural Sciences, Chosun University, Gwangju 501-759, Korea.
authors.forename: Jun Sik
authors.initials: JS
authors.lastname: Lee
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Lee
authors.forename: Tae Kwun
authors.initials: TK
authors.lastname: Ha
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Deok Rim
authors.initials: DR
authors.lastname: Heo
authors.forename: Kwang Hee
authors.initials: KH
authors.lastname: Son
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park