Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN

Jin Hee Kim, Tae Heung Kang, Kyung Hee Noh, Seok Ho Kim, Young Ho Lee, Keon Woo Kim, Hyun Cheol Bae, Ye Hyeon Ahn, Eun Young Choi, Jin Seok Kim, Kyung Mi Lee, Tae Woo Kim

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26 Citations (Scopus)

Abstract

Dendritic cell (DC)-based cancer vaccines have become important as an immunotherapeutics in generating anti-tumor immune responses. Due to a short lifespan of DCs, however, clinical application of current DC vaccines has been limited. Recently, activation of AKT/protein kinase B (PKB), a major effector of phosphatidylinositol 3-kinase (PI3K), has been reported as a critical factor in both activation and survival of DCs. We here improved the potency of a DC vaccine with a small interfering RNA (siRNA) targeting phosphatase and tensin homologue (PTEN), which is known to be a central negative regulator of the PI3K/AKT signal transduction cascade. Down-regulation of PTEN in DCs resulted in AKT dependent maturation, which in turn caused a significant up-regulation of surface expression in co-stimulatory molecules and the chemokine receptor, CCR7, leading to an increase of in vitro T cell activation activity and in vivo migration to a draining lymph node, respectively. Moreover, these PTEN siRNA-transfected DCs (DC/siPTEN) acquired an increased survival from the apoptotic death caused by GM-CSF deprivation or antigen-specific CD8+ T cell killing. Most importantly, DC/siPTEN generated more tumor antigen-specific CD8+ T cells and stronger anti-tumor effects in vaccinated mice than did control DCs (DC/siGFP). Thus, our data indicate that manipulation of the PI3K/AKT pathway via siRNA system could improve the efficacy of a DC-based tumor vaccine.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalImmunology Letters
Volume134
Issue number1
DOIs
Publication statusPublished - 2010 Nov 30

Keywords

  • AKT
  • Dendritic cell
  • Immunotherapy
  • PI3K
  • PTEN
  • SiRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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  • Cite this

    Kim, J. H., Kang, T. H., Noh, K. H., Kim, S. H., Lee, Y. H., Kim, K. W., Bae, H. C., Ahn, Y. H., Choi, E. Y., Kim, J. S., Lee, K. M., & Kim, T. W. (2010). Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN. Immunology Letters, 134(1), 47-54. https://doi.org/10.1016/j.imlet.2010.08.008