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

// Tae Heung Kang 1, * , Young Seob Kim 1, * , Seokho Kim 2, * , Benjamin Yang 6 , Je-Jung Lee 3 , Hyun-Ju Lee 3 , Jaemin Lee 2 , In Duk Jung 1 , Hee Dong Han 1 , Seung-Hyun Lee 4 , Sang Seok Koh 5 , T.-C. Wu 6, 7, 8, 9 , Yeong-Min Park 1 1 Department of Immunology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea 2 Aging Research Institute, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea 3 Research Center for Cancer Immunotherapy, Hwasun Hospital, Chonnam National University, Hwasun, Jeollanamdo, South Korea 4 Department of Microbiology, KU Open Innovation Center, School of Medicine, Konkuk University, Chungju, South Korea 5 Department of Biological Sciences, Dong-A University, Busan, South Korea 6 Departments of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA 7 Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA 8 Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA 9 Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA * These authors have contributed equally to this work Correspondence to: Sang Seok Koh, e-mail: sskoh@dau.ac.kr T.-C. Wu, e-mail: wutc@jhmi.edu Yeong-Min Park, e-mail: immun3023@kku.ac.kr Keywords: PAUF, dendritic cells, cancer vaccines, adjuvants, TLR4 Received: May 08, 2015      Accepted: July 27, 2015      Published: August 07, 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.