Deoxypodophyllotoxin Induces a Th1 Response and Enhances the Antitumor Efficacy of a Dendritic Cell-based Vaccine

• Published in: Immune network Vol. 11; no. 1; pp. 79 - 94
• Main 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
• Format: Journal Article
• Language: English
• Published: Korea (South) 대한면역학회 01.02.2011; The Korean Association of Immunologists
• Subjects: Original; 면역학; DC-based vaccination; Dendritic cells; CTL activity; Interleukin-12; Deoxypodophyllotoxin
• ISSN: 1598-2629; 2092-6685; 2092-6685
• DOI: 10.4110/in.2011.11.1.79

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. 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. 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. 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.