Maturation of dendritic cells by pullulan promotes anti-cancer effect
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Wei Zhang1,*, Xiaoqian Yu2,*, Minseok Kwak3,*, Li Xu1, LiJun Zhang1, Qing Yu4,5, Jun-O Jin1
1Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China
2Periodontal Department, Peking University School and Hospital of Stomatology, Beijing, China
3Department of Chemistry, Pukyong National University, Busan, South Korea
4Department of Immunology and Infectious Diseases, The Forsyth Institute, Cambridge, MA, USA
5Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA
*These authors have contributed equally to the work
Jun-O Jin, email: Junojin1@gmail.com
Keywords: pullulan, adjuvant, dendritic cell, immunotherapy, anti-cancer
Received: November 19, 2015 Accepted: May 17, 2016 Published: June 20, 2016
Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines.
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