Detection of immunogenic cell death and its relevance for cancer therapy.

Detection of immunogenic cell death and its relevance for cancer therapy.
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DOI:
10.1038/s41419-020-03221-2
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发表时间:
2020-11-26
影响因子:
9
通讯作者:
Galluzzi L
Galluzzi L
中科院分区:
生物学1区
文献类型:
--
作者:
Fucikova J;Kepp O;Kasikova L;Petroni G;Yamazaki T;Liu P;Zhao L;Spisek R;Kroemer G;Galluzzi L

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化学疗法、放射疗法以及靶向抗癌剂可以诱导临床相关的肿瘤靶向免疫应答,其严重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)伴随着许多损伤相关分子模式(DAMP)的暴露和释放,这些分子模式共同赋予垂死癌细胞强大的佐剂性,因为它们有利于抗原呈递细胞的募集和活化。ICD相关DAMP包括表面暴露钙网蛋白(CALR)以及分泌的ATP、膜联蛋白A1(ANXA 1)、I型干扰素和高迁移率族蛋白1(HMG B1)。ICD的其他标志包括真核翻译起始因子2亚基-α(EIF 2S 1,更好地称为eIF 2 α)的磷酸化,自噬的激活以及转录和翻译的全面停滞。在这里,我们概述了体外和离体测量ICD标记物的方法,用于发现下一代抗肿瘤药物,开发个性化抗癌方案,并确定癌症临床管理的最佳治疗组合。
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.
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