Abstract
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.
Highlights
In recent research on the development of therapeutic agents for cancer, the trend has been to search for candidates among natural products because they have relatively low or tolerable toxicity [1]
The results demonstrated that pullulan enhanced dendritic cells (DC) maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice
We determined whether pullulan induced the activation of bone marrow-derived DCs (BMDC) in vitro and of spleen conventional DCs (cDC) in vivo
Summary
In recent research on the development of therapeutic agents for cancer, the trend has been to search for candidates among natural products because they have relatively low or tolerable toxicity [1]. The present study was undertaken to test the hypothesis that pullulan is an effective adjuvant because it induces the activation of spleen cDCs and Ag-specific immune responses in vivo, promoting anti-cancer immunity. To determine whether the up-regulation of MHC class I and II expression on spleen DCs induced by the combination of OVA and pullulan can subsequently promote OVA-specific OT-I and OT-II T cell proliferation, we transferred CFSElabeled OT-I and OT-II T cells into CD45.1 congenic www.impactjournals.com/oncotarget mice.
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