传出细胞增多
癌症免疫疗法
免疫原性细胞死亡
先天免疫系统
免疫系统
癌细胞
癌症研究
免疫检查点
刺
免疫疗法
细胞生物学
癌症
生物
免疫学
巨噬细胞
体外
生物化学
遗传学
工程类
航空航天工程
作者
Zhian Chen,Zhenhao Li,Huilin Huang,Guodong Shen,Yingxin Ren,X. Mao,Lingzhi Wang,Zhenyuan Li,Weisheng Wang,Guoxin Li,Bingxia Zhao,Weihong Guo,Yanfeng Hu
出处
期刊:Small
[Wiley]
日期:2023-06-28
卷期号:19 (43)
被引量:13
标识
DOI:10.1002/smll.202302758
摘要
Innate immunity triggered by the cGAS/STING pathway has the potential to improve cancer immunotherapy. Previously, the authors reported that double-stranded DNA (dsDNA) released by dying tumor cells can trigger the cGAS/STING pathway. However, owing to efferocytosis, dying tumor cells are engulfed and cleared before the damaged dsDNA is released; hence, immunologic tolerance and immune escape occur. Herein, a cancer-cell-membrane biomimetic nanocomposites that exhibit tumor-immunotherapeutic effects are synthesized by augmenting the cGAS/STING pathway and suppressing efferocytosis. Once internalized by cancer cells, a combined chemo/chemodynamic therapy would be triggered, which damages their nuclear and mitochondrial DNA. Furthermore, the releasing Annexin A5 protein could inhibit efferocytosis effect and promote immunostimulatory secondary necrosis by preventing phosphatidylserine exposure, resulting in the burst release of dsDNA. These dsDNA fragments, as molecular patterns to immunogenic damage, escape from the cancer cells, activate the cGAS/STING pathway, enhance cross-presentation inside dendritic cells, and promote M1-polarization of tumor-associated macrophages. In vivo experiments suggest that the proposed nanocomposite could recruit cytotoxic T-cells and facilitate long-term immunological memory. Moreover, when combined with immune-checkpoint blockades, it could augment the immune response. Therefore, this novel biomimetic nanocomposite is a promising strategy for generating adaptive antitumor immune responses.
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