Sotio, Prague, Czech Republic.
2nd Faculty of Medicine and University Hospital Motol, Department of Immunology, Charles University, Prague, Czech Republic.
Cell Death Dis. 2020 Nov 26;11(11):1013. doi: 10.1038/s41419-020-03221-2.
Chemotherapy, radiation therapy, as well as targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which altogether confer a robust adjuvanticity to dying cancer cells, as they favor the recruitment and activation of antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) as well as secreted ATP, annexin A1 (ANXA1), type I interferon, and high-mobility group box 1 (HMGB1). Additional hallmarks of ICD encompass the phosphorylation of eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known as eIF2α), the activation of autophagy, and a global arrest in transcription and translation. Here, we outline methodological approaches for measuring ICD markers in vitro and ex vivo for the discovery of next-generation antineoplastic agents, the development of personalized anticancer regimens, and the identification of optimal therapeutic combinations for the clinical management of cancer.
化疗、放疗以及靶向抗癌药物能够诱导具有临床相关性的肿瘤靶向免疫反应,而这主要依赖于恶性细胞的抗原性及其产生佐剂信号的能力。特别是,免疫原性细胞死亡(ICD)伴随着大量损伤相关分子模式(DAMPs)的暴露和释放,这些 DAMPs 共同赋予垂死癌细胞强大的佐剂活性,因为它们有利于抗原呈递细胞的募集和激活。与 ICD 相关的 DAMPs 包括表面暴露的钙网蛋白(CALR)以及分泌的 ATP、膜联蛋白 A1(ANXA1)、I 型干扰素和高迁移率族蛋白 B1(HMGB1)。ICD 的其他特征还包括真核翻译起始因子 2 亚基-α(EIF2S1,也称为 eIF2α)的磷酸化、自噬的激活以及转录和翻译的全局停滞。在这里,我们概述了用于体外和离体测量 ICD 标志物的方法学方法,用于发现新一代抗肿瘤药物、开发个性化抗癌方案以及确定用于癌症临床管理的最佳治疗组合。
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