Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine.
- Author:
Jun Sik LEE
1
;
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
Author Information
- Publication Type:Original Article
- Keywords: Dendritic cells; Deoxypodophyllotoxin; Interleukin-12; CTL activity; DC-based vaccination
- MeSH: Animals; Dendritic Cells; Immunotherapy; Interleukin-12; Lymph Nodes; Lymphocyte Culture Test, Mixed; Lymphocytes; Mice; Phenotype; Podophyllotoxin; T-Lymphocytes; Toll-Like Receptors; Up-Regulation; Vaccination; Vaccines
- From:Immune Network 2011;11(1):79-94
- CountryRepublic of Korea
- Language:English
- 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-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.
