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The goal of cancer immunotherapy is to clear tumor cells by activating antitumor immunity, especially by mobilizing tumor-reactive CD8+T cells. Pyroptosis, programmed lytic cell death mediated by gasdermin (GSDM), results in the release of cellular antigens, damage-associated molecular patterns (DAMPs) and cytokines. Therefore, pyroptotic tumor cell-derived tumor antigens and DAMPs not only reverse immunosuppression of the tumor microenvironment (TME) but also enhance tumor antigen presentation by dendritic cells, leading to robust antitumor immunity. Exploring nanoparticles and other approaches to spatiotemporally control tumor pyroptosis by regulating gasdermin expression and activation is promising for next-generation immunotherapy. 相似文献
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Shi-Wei Liu Wen-Jing Song Gui-Kai Ma Hui Wang Liang Yang 《World Journal of Clinical Cases》2023,11(11):2386-2395
Programmed cell death (PCD) is mediated by specific genes that encode signals. It can balance cell survival and death. Pyroptosis is a type of inflammatory, caspase-dependent PCD mediated by gasdermin proteins, which function in pore formation, cell expansion, and plasma membrane rupture, followed by the release of intracellular contents. Pyroptosis is mediated by caspase-1/3/4/5/11 and is primarily divided into the classical pathway, which is dependent on caspase-1, and the non-classical pathway, which is dependent on caspase-4/5/11. Inflammasomes play a vital role in these processes. The various components of the pyroptosis pathway are related to the occurrence, invasion, and metastasis of tumors. Research on pyroptosis has revealed new options for tumor treatment. This article summarizes the recent research progress on the molecular mechanism of pyroptosis, the relationship between the various components of the pyroptosis pathway and cancer, and the applications and prospects of pyroptosis in anticancer therapy. 相似文献
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细胞程序性死亡是指细胞依赖于某些特定的基因编码信号或活动的死亡方式。细胞凋亡、自噬、胀亡、焦亡等均属于细胞程序性死亡。其中,焦亡是一种依赖含半胱氨酸的天冬氨酸蛋白水解酶(caspase)的细胞程序性死亡方式。近年来,国内外相关研究发现,焦亡与炎性疾病、自身免疫性疾病及肿瘤均有关系。充分了解焦亡发生的机制及其与肿瘤的关系,对肿瘤的治疗具有一定的指导意义。本文针对焦亡的相关机制及焦亡与头颈部肿瘤的相关研究进展进行综述。 相似文献
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《Immunobiology》2020,225(2):151884
Pyroptosis is a newly discovered untypical form of programmed cell death by inflammatory response, which is dependent on the classic pathway of Caspase-1 and the non-canonical pathway of Caspase-11 in mice or orthologue Caspase-4/-5 in Humans. It has been found that the Gasdermin family of protein is a key molecule in the formation of membrane pores of pyroptosis. After being cleaved by inflammatory caspases, it releases a N-terminal fragment with perforating activity to trigger pyroptosis. That pyroptosis is closely related to the occurrence and development of certain diseases. Now, the molecular mechanism of pyroptosis and pyroptosis-related diseases are reviewed. 相似文献
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《Immunity》2022,55(4):623-638.e5
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哮喘是一种由遗传和环境因素共同影响的常见的气道慢性炎性疾病,其分子遗传学基础复杂多样,目前临床上仍无疗效显著的治疗方法.全基因组相关联研究通过寻找哮喘发病机制的基因靶点,从分子遗传学角度为儿童哮喘的精准化医疗提供新思路.现研究证明17q21位点上血清类黏蛋白1样蛋白3基因(ORMDL3)和gasdermin B (GSMDB)基因的表达影响儿童哮喘的易患性、严重性、及种族特异性.该文对17q21染色体位点上与儿童哮喘相关的基因进行综述. 相似文献
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Hong Li Xue-Ke Zhao Yi-Ju Cheng Quan Zhang Jun Wu Shuang Lu Wei Zhang Yang Liu Ming-Yu Zhou Ya Wang Jing Yang Ming-Liang Cheng 《World journal of gastroenterology : WJG》2019,25(44):6527-6540
BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death. However, the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(sh RNA) was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1) and its receptor CC chemokine receptor-2(CCR2) in vitro. For in vivo experiments, we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALFpatients and a hepatocyte injury model increased significantly. The level of GSDMD-N protein increased most obviously(P 0.001). In vitro, downregulation of GSDMD by sh RNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P 0.01). In vivo, GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P 0.001). Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1β and IL-18, GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death. However, this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF, recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses. GSDMD knockout can reduce hepatocyte death and inflammatory responses, thus alleviating ALF. 相似文献