放射增敏剂
免疫抑制
放射治疗
免疫系统
表观遗传学
癌症研究
癌症
组蛋白脱乙酰基酶
组蛋白脱乙酰酶抑制剂
生物
组蛋白
医学
免疫学
内科学
DNA
生物化学
遗传学
基因
作者
Guohao Wang,Jie Yan,Hao Tian,Bei Li,Xinying Yu,Yuzhao Feng,Wenxi Li,Songtao Zhou,Yunlu Dai
标识
DOI:10.1002/adma.202312588
摘要
Abstract Cancer cells can upregulate the MYC expression to repair the radiotherapy‐triggered DNA damage, aggravating therapeutic resistance and tumor immunosuppression. Epigenetic treatment targeting the MYC‐transcriptional abnormality may intensively solve this clinical problem. Herein, we engineered 5‐Aza (a DNA methyltransferase inhibitor) and ITF‐2357 (a histone deacetylase inhibitor) into a tungsten‐based nano‐radiosensitizer (PWAI), to suppress MYC rising and awaken robust radiotherapeutic antitumor immunity. Individual 5‐Aza depletes MYC expression but cannot efficiently awaken radiotherapeutic immunity. This drawback can be overcome by the addition of ITF‐2357, which triggers cancer cellular type I interferon (IFN‐I) signaling. Coupling 5‐Aza with ITF‐2357 ensures that PWAI does not evoke the treated model with high MYC‐related immune resistance while amplifying the radiotherapeutic tumor killing, and more importantly promotes the generation of IFN‐I signal‐related proteins involving IFN‐α and IFN‐β. Unlike the radiation treatment alone, PWAI‐triggered immuno‐radiotherapy remarkably enhances anti‐tumor immune responses involving the tumor antigen presentation by dendritic cells, and improves intratumoral recruitment of cytotoxic T lymphocytes and their memory‐phenotype formation in 4T1 tumor‐bearing mice. Downgrading the radiotherapy‐induced MYC overexpression via the dual‐epigenetic reprogramming strategy may elicit a robust immuno‐radiotherapy. This article is protected by copyright. All rights reserved
科研通智能强力驱动
Strongly Powered by AbleSci AI