Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA, 30912, USA.
Department of Restorative Sciences, Dental College of Georgia, Augusta University, Augusta, GA, 30912, USA.
J Exp Clin Cancer Res. 2021 Aug 24;40(1):264. doi: 10.1186/s13046-021-02065-8.
Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.
肿瘤对细胞凋亡的抵抗和免疫抑制性肿瘤微环境是癌症干预过程中治疗反应不佳的两个主要原因。细胞焦亡,一种不同于细胞凋亡的裂解性和炎症性程序性细胞死亡途径,随后引起了癌症研究人员的极大兴趣,因为它有可能被临床利用并解决这些问题。最近的证据表明,肿瘤细胞中细胞焦亡的诱导导致强烈的炎症反应和明显的肿瘤消退。细胞焦亡通过形成孔的 gasdermin 蛋白介导其抗肿瘤作用,这些蛋白通过在细胞破裂后释放促炎细胞因子和免疫原性物质来促进免疫细胞的激活和浸润。然而,考虑到其炎症性质,异常的细胞焦亡也可能与肿瘤支持性微环境的形成有关,某些癌症中 gasdermin 蛋白的上调就是证据。在这篇综述中,介绍了导致细胞焦亡的分子途径,然后概述了细胞焦亡与癌症之间似乎纠缠不清的联系。我们描述了已知的细胞焦亡对抗肿瘤免疫的影响,并深入探讨了利用细胞焦亡作为一种工具并将其应用于新的或现有的抗肿瘤策略的潜力。
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