材料科学
免疫疗法
肿瘤微环境
放射治疗
功能(生物学)
癌症研究
业务流程重组
免疫系统
医学
内科学
免疫学
肿瘤细胞
化学工程
细胞生物学
生物
炼油厂
工程类
作者
Zetong Chen,Qing‐Yu He,Rui Qian,Jinzhou Cai,Ziqi Wang,Xuyi Zhou,Xinyang Zhang,Qiyun Wang,Hongwei Si,Jie Li,Kai Yang,Pei Pei
标识
DOI:10.1002/adfm.202502807
摘要
Abstract Analyzing the relationship between tumor O 2 microenvironment (TOME) and immune microenvironment during radiotherapy and regulating it will provide new insights into the combination of radiotherapy and immunotherapy. In the experiments, it is observed that the exacerbation of tumor hypoxia after radiotherapy activated the HIF pathway, which, in turn, led to T‐cell exhaustion by upregulating PD‐L1 expression in the tumor and promoting the infiltration of MDSCs. To address this, a manganese ion‐doped Au–Pt nanozyme‐coated O 2 modulator (Mn‐Nz‐M) is designed and prepared to reengineer the TOME. First, the high catalase activity of Mn‐Nz‐M efficiently generated O 2 at the tumor‐site, modulating the TOME and improving radiotherapy efficacy. More importantly, studies in vitro and in vivo showed that Mn‐Nz‐M‐mediated improvement of TOME can reverse PD‐1 + T cell exhaustion post radiotherapy and activate T cell function. Additionally, the Mn 2+ released from Mn‐Nz‐M can simultaneously amplify the cGAS‐STING pathway to activate NK cells for anti‐tumor activity. This reengineering strategy of the TOME for radio‐immunotherapy not only eliminates primary solid tumors but also inhibits tumor metastasis, providing new insights and potential therapeutic targets for enhancing the interaction between radiotherapy and immunotherapy.
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