GSDMs家族蛋白介导细胞焦亡在抗肿瘤免疫中的作用
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1)安徽省儿童医院临床药学部,合肥 230000;2)安徽医科大学基础医学院,合肥 230032;3)中国科学院合肥物质科学研究院健康与医学技术研究所,医学物理与技术安徽省重点实验室,合肥 230031;4)中国科学技术大学第一附属医院(安徽省立医院)胸外科,合肥 230001;5)皖南医学院基础医学院,芜湖 241002

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基金项目:

安徽医科大学校基金(2020xkj079) 和国家自然科学基金 (31970701) 资助项目。


The Role of Cell Pyroptosis Mediated by GSDMs in Antitumor Immunity
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Affiliation:

1)Clinical Pharmacy Department, Anhui Provincial Children’s Hospital, Hefei 230000, China;2)School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China;3)Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health & Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China;4)Department of Thoracic Surery, The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei 230001, China;5)College of Basic Medical Sciences, Wannan Medical College, Wuhu 241002, China

Fund Project:

This work was supported by grants from the Foundation of Anhui Medical University (2020xkj079) and The National Natural Science Foundation of China (31970701).

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    摘要:

    细胞焦亡是一种调节性细胞死亡方式。Gasdermine(GSDMs)是一类执行细胞焦亡的胞内蛋白质。虽然GSDMs表达后的完整蛋白质不具有活性,但能被某些蛋白水解酶激活。被激活的GSDMs N端在质膜上穿孔,导致细胞裂解,引起细胞内的促炎分子及损伤相关分子模式(danger-associated molecular patterns,DAMPs)迅速有效地从焦亡细胞中释放,从而引发炎症和免疫反应。焦亡细胞促进抗肿瘤免疫作用可能涉及细胞毒性T淋巴细胞对肿瘤细胞的杀伤。本文介绍GSDMs介导的细胞焦亡及细胞焦亡过程中引发促炎症和免疫反应的关键分子,并且探讨细胞焦亡对肿瘤治疗的有利及不利因素,以期更好地了解细胞焦亡对肿瘤免疫微环境的影响及对肿瘤免疫治疗的作用,有助于促进恶性肿瘤治疗策略的改进。

    Abstract:

    Pyroptosis, a type of regulated cell death, has been shown to be immunogenic in quite a few studies. Pyroptosis has been observed since 1986 and was found to be mediated by GSDM family proteins until recently. Gasdermines (GSDMs) are a group of intracellular proteins that mediates cell pyroptosis. Although GSDMs are expressed in inactive forms, some proteolytic enzymes can activate them. The N-terminus of activated GSDMs perforate the plasma membrane, resulting in cell lysis. Pyroptosis is a double-edged sword that is closely related to the tumor immune microenvironment. Pro-inflammatory molecules and DAMPs will be quickly and effectively released into the microenvironment from the pyroptotic cells, and trigger inflammation and immune response, while these immune responses are not always positive. Inductions of pyroptotic cell death have been shown to promote anti-tumor immunity and improve the efficacy of immune checkpoint inhibitors, which involves the cytotoxic effects of effector T lymphocytes, or reprogramming of the tumor microenvironment to an immunostimulatory state. In this review, we not only summarize the mechanisms of different types of pyroptosis and the key molecules that promote inflammatory and immune response during pyroptosis, but also compare its common features with apoptosis. In addition, we discuss the potential positive and negative factors to cancer therapy during pyroptosis. Although our understanding of pyroptosis in cancer is growing, many mechanisms remain unclear: how pyroptosis activates the immune system, how pyroptosis is regulated, and how pyroptosis can be harnessed therapeutically to improve cancer immunotherapy or to reduce therapy related toxicity. We hope this review will help further understanding the role of pyroptosis in tumor microenvironment and cancer immune therapy, promoting the improvement of cancer therapy strategies.

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季文博,李雲健,蔡和平,陈冠儒,田界勇,胡磊,戴海明,刘海鹏. GSDMs家族蛋白介导细胞焦亡在抗肿瘤免疫中的作用[J].生物化学与生物物理进展,2023,50(12):2807-2815

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历史
  • 收稿日期:2022-12-12
  • 最后修改日期:2023-11-01
  • 接受日期:2023-02-13
  • 在线发布日期: 2023-12-22
  • 出版日期: 2023-12-20