磷酸戊糖途径
癌症研究
烟酰胺腺嘌呤二核苷酸磷酸
CD8型
材料科学
免疫原性细胞死亡
接种疫苗
免疫系统
免疫疗法
生物
免疫学
生物化学
糖酵解
氧化酶试验
酶
作者
Yuxiang Wang,Jing Chen,Rumeng Duan,Rong Gu,Weiran Wang,Jinhui Wu,Huibo Lian,Yiqiao Hu,Ahu Yuan
标识
DOI:10.1002/adma.202109726
摘要
In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic tumor cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity for establishing efficient in situ vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor of the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) nanosheets to boost radiation-therapy (RT)-induced immunogenic cell death (ICD) for potent in situ tumor vaccination. It is first observed that sheet-like PLGdH can present superior X-ray deposition and tumor penetrability, exhibiting improved radiosensitization in vitro and in vivo. Moreover, the destruction of cellular nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotide homeostasis by Phy-mediated PPP intervention can further amplify PLGdH-sensitized RT-mediated oxidative stress and DNA damage, which correspondingly results in effective ICD and enhance the immunogenicity of irradiated tumor cells. Consequently, Phy@PLGdH-sensitized RT successfully primes robust CD8+ -T-cell-dependent antitumor immunity to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors.
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