肿瘤微环境
免疫系统
巨噬细胞极化
外体
GPX4
微泡
癌症研究
巨噬细胞
细胞生物学
氧化应激
生物
免疫学
谷胱甘肽过氧化物酶
小RNA
生物化学
基因
体外
过氧化氢酶
作者
Duo Wang,Guanhua Qiu,Xiaoqi Zhu,Qin Wang,Chunyan Zhu,Chao Fang,Junjie Liu,Kun Zhang,Yan Liu
标识
DOI:10.1136/jitc-2022-006516
摘要
Immunosuppressive tumor microenvironment (ITM) remains an obstacle that jeopardizes clinical immunotherapy.To address this concern, we have engineered an exosome inherited from M1-pheototype macrophages, which thereby retain functions and ingredients of the parent M1-phenotype macrophages. The delivered RSL3 that serves as a common ferroptosis inducer can reduce the levels of ferroptosis hallmarkers (eg, glutathione and glutathione peroxidase 4), break the redox homeostasis to magnify oxidative stress accumulation, promote the expression of ferroptosis-related proteins, and induce robust ferroptosis of tumor cells, accompanied with which systematic immune response activation can bbe realized. M1 macrophage-derived exosomes can inherit more functions and genetic substances than nanovesicles since nanovesicles inevitably suffer from substance and function loss caused by extrusion-arised structural damage.Inspired by it, spontaneous homing to tumor and M2-like macrophage polarization into M1-like ones are attained, which not only significantly magnify oxidative stress but also mitigate ITM including M2-like macrophage polarization and regulatory T cell decrease, and regulate death pathways.All these actions accomplish a synergistic antitumor enhancement against tumor progression, thus paving a general route to mitigate ITM, activate immune responses, and magnify ferroptosis.
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