RESULTS λ-CGN enhances DC maturation and cytokine production Moreover, CGN stimulated DCs pulsed with human papillomavirus (HPV) peptides induced strong HPV-specific CD8 + T cell responses and greatly inhibited tumor growth in TC-1 tumor mouse model. Here, we found that CGN could enhance DC maturation and cytokine production through TLR4 signaling pathway. However, it is still elusive whether CGN can regulate the maturation and function of DCs, and as adjuvant enhance the antitumor effect of DC-based vaccine. Several studies also reported that CGN has adjuvant effect on the enhancement of immune responses induced by peptide/protein-based vaccines. Recently, accumulating evidence has been shown that CGN has antitumor and immunomodulatory activities through toll-like receptor (TLR) 4 signaling pathway. CGN has been widely used as a food additive in various kinds of foods, such as infant formula, and its safety has been confirmed by a large body of animal subchronic and chronic toxicity studies. According to the number and the position of sulfated ester, CGNs are mainly classified into three groups including kappa (κ)-, iota (ι)-, and lambda (λ)-CGNs. Lots of efforts were focused on the development of safe and effective adjuvants.Ĭarrageenans (CGNs) are mucopolysaccharides with high molecular weight from marine red seaweeds, which contained β-1,4 and α-1,3 glycosidic linkages. Due to the safety, only a few of adjuvants including aluminum salts, MF59, AS03, AF03 and AS04 have been approved for use in human vaccines in the US and/or Europe. However, the clinical efficacy of DC-based vaccines remains to be improved.Īdjuvant can be used to enhance the immunogenicity of various kinds of vaccines through different mechanisms, such as depot formation, induction of cytokines and chemokines, increase of antigen uptake, improvement of APC maturation and antigen presentation. Clinical trials of DC-based vaccines carried out in tumor patients have been proved its safety and capacity in the induction of antigen-specific immune responses. Therefore, DCs as antigen carrier were considered promising vaccine platform against tumors. IL-12 secreted by DCs promotes the induction of CD4 + Th1 cells and cytotoxic T lymphocytes (CTL) to suppress tumor growth. The activation status of DCs including the expression of co-stimulatory molecules and MHC I/II, and the secretion of cytokines determined the differentiation of CD4 + helper T cell (Th) subsets and CD8 + T cell responses. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.ĭendritic cells (DCs), as professional antigen presenting cells (APCs), can capture, process and present antigens to naïve T cells to activate antigen-specific immune responses. Further, HPV-CGN-DC induced strong CD8 + T cell responses, which are negatively correlated with tumor volumes. The frequencies of CD4 + and CD8 + T cells in spleens of tumor mice and their activation status were significantly increased in HPV-CGN-DC group, but the frequencies of natural regulatory T cells and CD11b +Gr-1 + cells were significantly decreased. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. In this study, we investigated the effect of λ-carrageenan on the maturation and function of dendritic cells (DCs) and its adjuvant effect on DC-based vaccine. Received: NovemAccepted: JanuPublished: February 22, 2017 Keywords: λ-carrageenan, TLR4, dendritic cell-based vaccine, cancer immunotherapy, cellular responses Jinyao Li 1, 2, 3, Adila Aipire 2, Jinyu Li 2, Hongge Zhu 1, Yanping Wang 4, Wenjia Guo 1, Xiaoqin Li 1, Jia Yang 1, Chunling Liu 1ġAffiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011, ChinaĢCollege of Life Science and Technology, Xinjiang University, Urumqi 830046, ChinaģXinJiang DingJu Biotech CO., LTD, Urumqi 830000, ChinaĤBayin Guoleng Vocational and Technical College, Korla 841000, China
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