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细胞焦亡:抗肿瘤治疗的新策略。

Pyroptosis: a new paradigm of cell death for fighting against cancer.

机构信息

Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Tongzipo Road, Changsha, 410013, Hunan, China.

NHC Key Laboratory of Carcinogenesis, The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, 410078, Hunan, China.

出版信息

J Exp Clin Cancer Res. 2021 May 3;40(1):153. doi: 10.1186/s13046-021-01959-x.

Abstract

BACKGROUND

Unraveling the mystery of cell death is one of the most fundamental progresses of life sciences during the past decades. Regulated cell death (RCD) or programmed cell death (PCD) is not only essential in embryonic development, but also plays an important role in the occurrence and progression of diseases, especially cancers. Escaping of cell death is one of hallmarks of cancer.

MAIN BODY

Pyroptosis is an inflammatory cell death usually caused by microbial infection, accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). Gasdermin family proteins are the executors of pyroptosis. Cytotoxic N-terminal of gasdermins generated from caspases or granzymes proteases mediated cleavage of gasdermin proteins oligomerizes and forms pore across cell membrane, leading to release of IL-1β, IL-18. Pyroptosis exerts tumor suppression function and evokes anti-tumor immune responses. Therapeutic regimens, including chemotherapy, radiotherapy, targeted therapy and immune therapy, induce pyroptosis in cancer, which potentiate local and systemic anti-tumor immunity. On the other hand, pyroptosis of normal cells attributes to side effects of anti-cancer therapies.

CONCLUSION

In this review, we focus on the regulatory mechanisms of pyroptosis and the tumor suppressive function of pyroptosis. We discuss the attribution of pyroptosis in reprogramming tumor microenvironments and restoration of anti-tumor immunity and its potential application in cancer immune therapy.

摘要

背景

在过去几十年中,揭示细胞死亡的奥秘是生命科学最基础的进展之一。细胞程序性死亡(PCD)不仅在胚胎发育中必不可少,而且在疾病的发生和发展中也起着重要作用,尤其是癌症。细胞逃避程序性死亡是癌症的特征之一。

主要内容

细胞焦亡是一种通常由微生物感染引起的炎症性细胞死亡,伴随着炎性小体的激活和促炎细胞因子白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的成熟。Gasdermin 家族蛋白是细胞焦亡的执行者。Gasdermin 蛋白由半胱氨酸天冬氨酸蛋白酶(caspases)或颗粒酶介导的裂解产生的细胞毒性 N 端切割,形成寡聚体并在细胞膜上形成孔,导致 IL-1β、IL-18 的释放。细胞焦亡具有肿瘤抑制功能,并引发抗肿瘤免疫反应。化疗、放疗、靶向治疗和免疫治疗等治疗方案在癌症中诱导细胞焦亡,增强局部和全身抗肿瘤免疫。另一方面,正常细胞的细胞焦亡归因于抗肿瘤治疗的副作用。

结论

在这篇综述中,我们重点介绍了细胞焦亡的调控机制及其在肿瘤抑制中的功能。我们讨论了细胞焦亡在重塑肿瘤微环境和恢复抗肿瘤免疫中的作用及其在癌症免疫治疗中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b34/8091792/9163d8ca13f6/13046_2021_1959_Fig1_HTML.jpg

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