肿瘤微环境
免疫系统
癌症免疫疗法
免疫疗法
癌症研究
细胞毒性T细胞
获得性免疫系统
先天免疫系统
CD8型
免疫原性细胞死亡
免疫
化学
免疫学
生物
生物化学
体外
作者
Yuxuan Peng,Yukui Zhang,Dan Liu,Kongshuo Ma,Kaiqing Yun,Mengli Zhou,Linna Hai,Mengdi Xu,Yiyang Chen,Zhaohui Wang
标识
DOI:10.1002/advs.202403347
摘要
Abstract The highly immunosuppressive tumor microenvironment (TME) restricts the efficient activation of immune responses. To restore the surveillance of the immune system for robust activation, vast efforts are devoted to normalizing the TME. Here, a manganese‐doped layered double hydroxide (Mn‐LDH) is developed for potent anti‐tumor immunity by reversing TME. Mn‐LDH is synthesized via a one‐step hydrothermal method. In addition to the inherent proton neutralization capacity of LDH, the introduction of manganese oxide endows LDH with an additional ability to produce oxygen. Mn‐LDH effectively releases Mn 2+ and Mg 2+ upon exposure to TME with high levels of H + and H 2 O 2 , which activates synthase‐stimulator of interferon genes pathway and maintains the cytotoxicity of CD8 + T cells respectively, achieving a cascade‐like role in innate and adaptive immunity. The locally administered Mn‐LDH facilitated a “hot” network consisting of mature dendritic cells, M1‐phenotype macrophages, as well as cytotoxic and helper T cells, significantly inhibiting the growth of primary and distal tumors. Moreover, the photothermal conversion capacity of Mn‐LDH sparks more robust therapeutic effects in large established tumor models with a single administration and irradiation. Overall, this study guides the rational design of TME‐modulating immunotherapeutics for robust immune activation, providing a clinical candidate for next‐generation cancer immunotherapy.
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