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

Oncotarget
Tae Heung KangYeong-Min Park

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 Toll-like 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.

References

Jan 15, 2003·Journal of Leukocyte Biology·Ian D DavisJonathan Cebon
May 4, 2004·Nature Medicine·Carl G FigdorCornelis J M Melief
Apr 2, 2005·Nature Reviews. Immunology·Jacques Banchereau, A Karolina Palucka
Apr 19, 2007·Cancer Immunology, Immunotherapy : CII·Ji-Yan LiuYi-Xin Zeng
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Oct 11, 2011·Journal of Hepato-biliary-pancreatic Sciences·Hisahito EndoMitsukazu Gotoh
Dec 27, 2011·Age·Henryk F Urbanski, Krystina G Sorwell
Jul 6, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·In Duk JungYeong-Min Park
Aug 16, 2014·Journal of Translational Medicine·Rebecca SaenzDavorka Messmer

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Citations

Apr 2, 2019·Clinical and Translational Medicine·S K DanielV G Pillarisetty
Jun 2, 2016·Human Vaccines & Immunotherapeutics·Jennifer D ElsterKenneth G Lucas
Oct 17, 2017·Oncotarget·Jing LiXiubao Ren
Dec 19, 2020·Open Medicine·Haotian LuYing Liu
Dec 11, 2020·Experimental & Molecular Medicine·Gun-Young JangYeong-Min Park
Mar 25, 2020·Life Sciences·Mahsa SadeghzadehDariush Shanehbandi

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Methods Mentioned

BETA
ELISA
flow cytometry
density gradient centrifugation
protein assay
biosensor

Software Mentioned

Win MDI
BLItz

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