Pancreatic adenocarcinoma upregulated factor serves as adjuvant by activating dendritic cells through stimulation of TLR4

Tae Heung Kang, Young Seob Kim, Seokho Kim, Benjamin Yang, Je Jung Lee, Hyun Ju Lee, Jaemin Lee, In Duk Jung, Hee Dong Han, Seung Hyun Lee, Sang Seok Koh, T. C. Wu, Yeong Min Park

Research output: Contribution to journalArticle

Abstract

Dendritic cell (DC) based cancer vaccines represent a promising immunotherapeutic strategy against cancer. To enhance the modest immunogenicity of DC vaccines, various adjuvants are often incorporated. Particularly, most of the common adjuvants are derived from bacteria. In the current study, we evaluate the use of a human pancreatic cancer derived protein, pancreatic adenocarcinoma upregulated factor (PAUF), as a novel DC vaccine adjuvant. We show that PAUF can induce activation and maturation of DCs and activate NFkB by stimulating the Tolllike receptor signaling pathway. Furthermore, vaccination with PAUF treated DCs pulsed with E7 or OVA peptides leads to generation of E7 or OVA-specific CD8+ T cells and memory T cells, which correlate with long term tumor protection and antitumor effects against TC-1 and EG.7 tumors in mice. Finally, we demonstrated that PAUF mediated DC activation and immune stimulation are dependent on TLR4. Our data provides evidence supporting PAUF as a promising adjuvant for DC based therapies, which can be applied in conjunction with other cancer therapies. Most importantly, our results serve as a reference for future investigation of human based adjuvants.

Original languageEnglish (US)
Pages (from-to)27751-27762
Number of pages12
JournalOncotarget
Volume6
Issue number29
DOIs
StatePublished - Jan 1 2015

Keywords

  • Adjuvants
  • Cancer vaccines
  • Dendritic cells
  • PAUF
  • TLR4

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Kang, T. H., Kim, Y. S., Kim, S., Yang, B., Lee, J. J., Lee, H. J., Lee, J., Jung, I. D., Han, H. D., Lee, S. H., Koh, S. S., Wu, T. C., & Park, Y. M. (2015). Pancreatic adenocarcinoma upregulated factor serves as adjuvant by activating dendritic cells through stimulation of TLR4. Oncotarget, 6(29), 27751-27762. https://doi.org/10.18632/oncotarget.4859