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An ER‐Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non‐Small‐Cell Lung Cancer
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-11-20 , DOI: 10.1002/anie.202013987 Lili Wang 1 , Ruilin Guan 1 , Lina Xie 1 , Xinxing Liao 1 , Kai Xiong 1 , Thomas W. Rees 1 , Yu Chen 1 , Liangnian Ji 1 , Hui Chao 1
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-11-20 , DOI: 10.1002/anie.202013987 Lili Wang 1 , Ruilin Guan 1 , Lina Xie 1 , Xinxing Liao 1 , Kai Xiong 1 , Thomas W. Rees 1 , Yu Chen 1 , Liangnian Ji 1 , Hui Chao 1
Affiliation
Immunogenic cell death (ICD) is a vital component of therapeutically induced anti‐tumor immunity. An iridium(III) complex (Ir1), containing an N,N‐bis(2‐chloroethyl)‐azane derivate, as an endoplasmic reticulum‐localized ICD inducer for non‐small cell lung cancer (NSCLC) is reported. The characteristic discharge of damage‐associated molecular patterns (DAMPs), that is, cell surface exposure of calreticulin (CRT), extracellular exclusion of high mobility group box 1 (HMGB1), and ATP, were generated by Ir1 in A549 lung cancer cells, accompanied by an increase in endoplasmic reticulum stress and reactive oxygen species (ROS). The vaccination of immunocompetent mice with Ir1‐treated dying cells elicited an antitumor CD8+ T cell response and Foxp3+ T cell depletion, which eventually resulted in long‐acting anti‐tumor immunity by the activation of ICD in lung cancer cells. Ir1 is the first Ir‐based complex that is capable of developing an immunomodulatory response by immunogenic cell death.
中文翻译:
靶向ER的铱(III)复合物在非小细胞肺癌中诱导免疫原性细胞死亡
免疫原性细胞死亡(ICD)是治疗性诱导的抗肿瘤免疫力的重要组成部分。据报道,铱(III)络合物(Ir1)含有N,N-双(2-氯乙基)-氮杂烷衍生物,可作为内质网局部ICD诱导物用于非小细胞肺癌(NSCLC)。Ir1在A549肺癌细胞中产生损伤相关分子模式(DAMP)的特征放电,即钙网蛋白(CRT)的细胞表面暴露,高迁移率族盒1(HMGB1)和ATP的细胞外排斥,伴随着内质网应激和活性氧(ROS)的增加。用Ir1免疫免疫小鼠经过处理的垂死细胞引发抗肿瘤CD8 + T细胞应答和Foxp3 + T细胞耗竭,最终通过激活ICD激活肺癌细胞,从而产生长效抗肿瘤免疫力。Ir1是第一个能够通过免疫原性细胞死亡产生免疫调节反应的基于Ir的复合物。
更新日期:2020-11-20
中文翻译:
靶向ER的铱(III)复合物在非小细胞肺癌中诱导免疫原性细胞死亡
免疫原性细胞死亡(ICD)是治疗性诱导的抗肿瘤免疫力的重要组成部分。据报道,铱(III)络合物(Ir1)含有N,N-双(2-氯乙基)-氮杂烷衍生物,可作为内质网局部ICD诱导物用于非小细胞肺癌(NSCLC)。Ir1在A549肺癌细胞中产生损伤相关分子模式(DAMP)的特征放电,即钙网蛋白(CRT)的细胞表面暴露,高迁移率族盒1(HMGB1)和ATP的细胞外排斥,伴随着内质网应激和活性氧(ROS)的增加。用Ir1免疫免疫小鼠经过处理的垂死细胞引发抗肿瘤CD8 + T细胞应答和Foxp3 + T细胞耗竭,最终通过激活ICD激活肺癌细胞,从而产生长效抗肿瘤免疫力。Ir1是第一个能够通过免疫原性细胞死亡产生免疫调节反应的基于Ir的复合物。