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Pancreatic adenocarcinoma upregulated factor serves as adjuvant by activating dendritic cells through stimulation of TLR4
- Source :
- Oncotarget
- Publication Year :
- 2015
-
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.
- Subjects :
- medicine.medical_treatment
Papillomavirus E7 Proteins
Biology
Adenocarcinoma
CD8-Positive T-Lymphocytes
Cancer Vaccines
Monocytes
Mice
Adjuvants, Immunologic
Pancreatic cancer
Cell Line, Tumor
Lectins
medicine
Animals
Humans
dendritic cells
TLR4
Mice, Knockout
Immunogenicity
Cancer
NF-kappa B p50 Subunit
Dendritic cell
medicine.disease
Flow Cytometry
3. Good health
Up-Regulation
Mice, Inbred C57BL
Pancreatic Neoplasms
Toll-Like Receptor 4
Oncology
adjuvants
Immunology
Intercellular Signaling Peptides and Proteins
Female
Peptides
PAUF
Adjuvant
Immunologic Memory
CD8
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 6
- Issue :
- 29
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....9e356b55496b5171a3ed7252395b6d48