通过肿瘤微粒疫苗改编的单核细胞能够抑制肿瘤发生和发展。
Monocytes reprogrammed by tumor microparticle vaccine inhibit tumorigenesis and tumor development.
发表日期:2023
作者:
Weiwei Sun, Lili Dai, Yuqing Cao, Pengtao Pan, Lijuan Zhi, Xinke Wang, Xinzhong Yuan, Zi Gao, Sheng Guo, Guoyan Liu, Junlei Yin, Liangliang Xie, Liping Wang, Yanling Wang, Wensheng Li, Hong Li, Yunjie Jia
来源:
Cancer Nanotechnology
摘要:
肿瘤微粒子(T-MPs)被视为肿瘤疫苗候选物。尽管一些研究已经分析了T-MPs作为肿瘤疫苗的机制,但我们仍然缺乏对T-MPs如何刺激强烈的抗肿瘤免疫反应的理解。在这里,我们展示T-MPs能够诱导巨噬细胞释放一个关键的趋化因子CCL2,这个趋化因子会吸引单核细胞到疫苗注射部位并增强抗原的内吞作用。单核细胞随后进入引流淋巴结,并分化成单核细胞源性树突状细胞(moDCs),将肿瘤抗原呈递给T淋巴细胞并传递强效的抗肿瘤免疫反应。机械地说,T-MPs通过DNA片段激活cGAS-STING信号通路,然后诱导单核细胞上调IRF4的表达,IRF4是单核细胞分化为moDCs的关键因子。更重要的是,内吞T-MPs的单核细胞获得了治疗肿瘤的能力。总的来说,这项工作可能为肿瘤疫苗的开发提供新的接种策略,并促进T-MPs在临床肿瘤治疗中的应用。此在线版本包含可在10.1186/s12645-023-00190-x中获得的补充材料。© 作者(们)2023。
Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy.The online version contains supplementary material available at 10.1186/s12645-023-00190-x.© The Author(s) 2023.