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免疫原性细胞死亡、损伤相关分子模式与胸腺素α原作为一种潜在的抗癌免疫反应生物标志物

Immunogenic Cell Death, DAMPs and Prothymosin α as a Putative Anticancer Immune Response Biomarker.

作者信息

Birmpilis Anastasios I, Paschalis Antonios, Mourkakis Apostolis, Christodoulou Panayiota, Kostopoulos Ioannis V, Antimissari Elina, Terzoudi Georgia, Georgakilas Alexandros G, Armpilia Christina, Papageorgis Panagiotis, Kastritis Efstathios, Terpos Evangelos, Dimopoulos Meletios A, Kalbacher Hubert, Livaniou Evangelia, Christodoulou Maria-Ioanna, Tsitsilonis Ourania E

机构信息

Section of Animal and Human Physiology, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Ilissia, 15784 Athens, Greece.

DNA Damage Laboratory, Physics Department, School of Mathematical and Physical Sciences, National Technical University of Athens, 15780 Zografou, Greece.

出版信息

Cells. 2022 Apr 22;11(9):1415. doi: 10.3390/cells11091415.


DOI:10.3390/cells11091415
PMID:35563721
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9102069/
Abstract

The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. Thus, several members of the DAMP family, such as the well-characterized heat shock proteins (HSPs) HSP70 and HSP90, the high-mobility group box 1 protein and calreticulin, and the thymic polypeptide prothymosin α (proTα) and its immunoreactive fragment proTα(100-109), are being studied as potential diagnostic tools and/or possible therapeutic agents. Here, we present the basic aspects and mechanisms of both ICD and other immunogenic RCD forms; denote the role of DAMPs in ICD; and further exploit the relevance of human proTα and proTα(100-109) in ICD, highlighting their possible clinical applications. Furthermore, we present the preliminary results of our in vitro studies, which show a direct correlation between the concentration of proTα/proTα(100-109) and the levels of cancer cell apoptosis, induced by anticancer agents and γ-radiation.

摘要

免疫原性细胞死亡(ICD)这一全新且研究日益深入的概念揭示了各种程序性细胞死亡(RCD)方式此前未知的一面,阐明了它们的免疫原性特性,使免疫刺激仅是坏死结果这一观念过时。ICD的一个显著特征是垂死和/或死亡细胞释放危险相关分子模式(DAMPs)。因此,DAMP家族的几个成员,如特征明确的热休克蛋白(HSPs)HSP70和HSP90、高迁移率族蛋白B1和钙网蛋白,以及胸腺多肽原胸腺素α(proTα)及其免疫反应性片段proTα(100 - 109),正作为潜在的诊断工具和/或可能的治疗药物进行研究。在此,我们介绍ICD和其他免疫原性RCD形式的基本方面和机制;指出DAMPs在ICD中的作用;并进一步探讨人proTα和proTα(100 - 109)在ICD中的相关性,突出它们可能的临床应用。此外,我们展示了体外研究的初步结果,这些结果表明proTα/proTα(100 - 109)的浓度与抗癌药物和γ射线诱导的癌细胞凋亡水平之间存在直接相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/e8dc876d7f80/cells-11-01415-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/5cd3a3af2d03/cells-11-01415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/d6fa3d1841b8/cells-11-01415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/82f6a39a6b0d/cells-11-01415-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/a285b7dabd53/cells-11-01415-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/e8dc876d7f80/cells-11-01415-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/5cd3a3af2d03/cells-11-01415-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/d6fa3d1841b8/cells-11-01415-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/82f6a39a6b0d/cells-11-01415-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/a285b7dabd53/cells-11-01415-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eaa6/9102069/e8dc876d7f80/cells-11-01415-g005.jpg

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