Li Jinyao, Aipire Adila, Li Jinyu, Zhu Hongge, Wang Yanping, Guo Wenjia, Li Xiaoqin, Yang Jia, Liu Chunling
Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830011, China.
College of Life Science and Technology, Xinjiang University, Urumqi 830046, China.
Oncotarget. 2017 May 2;8(18):29996-30007. doi: 10.18632/oncotarget.15610.
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. We found that λ-carrageenan dose-dependently decreased the endocytosis of DCs, promoted DC maturation and increased cytokine production through TLR4 mediated signaling pathway. λ-carrageenan treatment also enhanced the ability of DCs in the stimulating allogenic splenocyte proliferation. In TC-1 tumor mouse model, HPV peptides pulsed λ-carrageenan-DC (HPV-CGN-DC) significantly inhibited tumor growth compared with control group. 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. Further, HPV-CGN-DC induced strong CD8+ T cell responses, which are negatively correlated with tumor volumes. The results suggested that λ-carrageenan promoted DC maturation through TLR4 signaling pathway and could be used as the adjuvant in DC-based vaccines.
在本研究中,我们探究了λ-卡拉胶对树突状细胞(DCs)成熟和功能的影响及其对基于DC的疫苗的佐剂效应。我们发现,λ-卡拉胶剂量依赖性地降低DCs的内吞作用,通过Toll样受体4(TLR4)介导的信号通路促进DC成熟并增加细胞因子产生。λ-卡拉胶处理还增强了DCs刺激同种异体脾细胞增殖的能力。在TC-1肿瘤小鼠模型中,与人乳头瘤病毒(HPV)肽脉冲处理的λ-卡拉胶-DC(HPV-CGN-DC)相比,对照组肿瘤生长显著受到抑制。HPV-CGN-DC组肿瘤小鼠脾脏中CD4+和CD8+ T细胞的频率及其活化状态显著增加,但自然调节性T细胞和CD11b+Gr-1+细胞的频率显著降低。此外,HPV-CGN-DC诱导强烈的CD8+ T细胞反应,这与肿瘤体积呈负相关。结果表明,λ-卡拉胶通过TLR4信号通路促进DC成熟,可作为基于DC的疫苗的佐剂。