PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
基于重组乳酸乳球菌制备的树突状细胞疫苗通过 ROS 产生增强抗原交叉呈递和抗肿瘤疗效
英文原题：Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis enhances antigen cross-presentation and antitumor efficacy through ROS production.
查看英文原题
Dendritic cell-based vaccine prepared with recombinant Lactococcus lactis enhances antigen cross-presentation and antitumor efficacy through ROS production.
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研究概要
本研究表明，重组 L.L 作为抗原递送系统制备的 DC 疫苗能够增强抗原交叉呈递和抗肿瘤效果。
研究思路结论见上方概要
背景
乳酸乳球菌（L.L）是安全的，可作为载体使用。本研究探讨了L.L对树突状细胞（DC）活化的免疫调节作用及其机制。研究了用OVA重组L.L制备的DC疫苗的免疫应答和抗原交叉呈递机制。
方法
采用共聚焦显微镜和流式细胞术分析L.L促进DC成熟、吞噬体膜破裂及抗原提呈的机制。在B16-OVA肿瘤小鼠模型中评估了用L.L-OVA制备的DC疫苗的抗肿瘤效果。
结果
L.L显著促进DC成熟，这一作用部分依赖于TLR2及其下游MAPK和NF-κB信号通路。L.L通过内吞作用被内化进入DCs，且不与溶酶体共定位。OVA重组L.L通过吞噬体至胞质途径以活性氧（ROS）和蛋白酶体依赖的方式增强DCs的抗原交叉呈递。在小鼠实验中，L.L增加了DCs向引流淋巴结的迁移，用OVA重组L.L制备的DC疫苗诱导了强烈的抗原特异性Th1和细胞毒性T淋巴细胞反应，显著抑制了B16-OVA肿瘤生长。
展开英文摘要原文
METHODS
Confocal microscopy and flow cytometry were used to analyze the mechanism of L.L promoting DC maturation, phagosome membrane rupture and antigen presentation. The antitumor effect of DC vaccine prepared with L.L-OVA was assessed in the B16-OVA tumor mouse model.
RESULTS
L.L significantly promoted DC maturation, which was partially dependent on TLR2 and downstream MAPK and NF-κB signaling pathways. L.L was internalized into DCs by endocytosis and did not co-localized with lysosome. OVA recombinant L.L enhanced antigen cross-presentation of DCs through the phagosome-to-cytosol pathway in a reactive oxygen species (ROS)- and proteasome-dependent manner. In mouse experiments, L.L increased the migration of DCs to draining lymph node and DC vaccine prepared with OVA recombinant L.L induced strong antigen-specific Th1 and cytotoxic T lymphocyte responses, which significantly inhibited B16-OVA tumor growth.
CONCLUSION
This study demonstrated that recombinant L.L as an antigen delivery system prepared DC vaccine can enhance the antigen cross-presentation and antitumor efficacy.
论文信息
- 作者
- Zhang T、Wei X、Li Y、Huang S、Wu Y、Cai S、Aipire A、Li J
- 单位
- Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Frontiers in immunology2023
- 原文标识
- PubMed 37711617 · DOI 10.3389/fimmu.2023.1208349
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