背向效应
癌症研究
肿瘤微环境
免疫疗法
免疫原性细胞死亡
免疫系统
TLR9型
癌症免疫疗法
免疫检查点
CpG寡核苷酸
医学
免疫学
生物
DNA甲基化
基因表达
基因
生物化学
作者
Yuhua Cao,Shuaishuai Ding,Lijuan Zeng,Jingya Miao,Kai Wang,Gang Chen,Chunyan Li,Jingrong Zhou,Xiu‐Wu Bian,Gan Tian
标识
DOI:10.1021/acsami.1c07626
摘要
With the recent success of immune checkpoint blockade (ICB) in cancer immunotherapy, there has been renewed interest in evaluating the combination of ICB inhibitors with radiotherapy (RT) in clinical trials in view of the localized RT-initiated vaccination effect, which can be augmented further by systemic immune-stimulating agents. Unfortunately, traditional RT/ICB accompanies severe toxicity from high-dose ionizing irradiation and low response rate from RT-aggravated immunosuppression, among which M2-type tumor-associated macrophages (TAMs) play an important role. Herein, CpG-decorated gold (Au) nanoparticles (CpG@Au NPs) were fabricated to improve the RT/ICB efficacy by immune modulation under low-dose X-ray exposure, where Au NPs served as radioenhancers to minimize the radiotoxicity, and yet acted as nanocarriers to deliver CpG, a toll-like receptor 9 agonist, to re-educate immunosuppressive M2 TAMs to immunostimulatory M1 counterparts, thus arousing innate immunity and meanwhile priming T cell activation. When combined with an anti-programmed death 1 antibody, irradiated CpG@Au led to consistent abscopal responses that efficiently suppressed distant tumors in a bilateral GL261 tumor-bearing model. This work thus demonstrates that CpG@Au-mediated macrophage reeducation could efficiently modulate the tumor-immune microenvironment for synergistic RT/ICB.
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