中山大学化学学院巢晖研究团队发现，一种内质网靶向的铱(III)复合物可在非小细胞肺癌中诱导免疫原性细胞死亡。 相关论文于2020年11月20日发表于国际顶尖学术期刊《德国应用化学》上。

免疫原性细胞死亡（ICD）是治疗引发的抗肿瘤免疫的关键组成部分。该文章报道了一种包含N,N‐bis(2‐chloroethyl)‐azane的铱(III)复合物（Ir1），作为非小细胞肺癌（NSCLC）内质网定位的ICD诱导剂。Ir1处理后的A549肺癌细胞表现出典型的损伤相关分子模式（DAMPs），包括钙网蛋白在细胞表面暴露，高迁移率族蛋白（HMGB1）和ATP外排等。免疫健全小鼠在接种Ir1处理过的死亡细胞后可诱发抗肿瘤CD8⁺ T细胞应答和Foxp3⁺ T细胞耗竭，最终通过激活肺癌细胞中的ICD产生长效的抗肿瘤免疫。

研究人员表示，对非小细胞肺癌同时具备诱导ICD和常规化疗作用的Ir1分子是一种很有潜力的抗癌药物。据他们所知，Ir1是第一种能够通过免疫原性细胞死亡而产生免疫调节活性的铱基复合物。

附：英文原文

Title: An ER‐Targeting Iridium(III) Complex which Induces Immunogenic Cell Death in Non‐Small Cell Lung Cancer

Author: Hui Chao, Lili Wang, Ruilin Guan, Lina Xie, Xinxing Liao, Kai Xiong, Thomas W. Rees, Yu Chen, Liangnian Ji

Issue&Volume: 20 November 2020

Abstract: 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 herein reported. The characteristic discharge of damage‐associated molecular patterns (DAMPs), i.e. 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. With the dual actions of ICD and chemotherapy against NSCLC,  Ir1  has great potential as an antitumor agent. To the best of our knowledge,  Ir1  is the first iridium‐based complex that is capable of developing an immunomodulatory response by immunogenic cell death.

DOI: 10.1002/anie.202013987

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202013987