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细胞焦亡在抗肿瘤免疫中处于前沿地位。

Pyroptosis at the forefront of anticancer immunity.

机构信息

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.

出版信息

J Exp Clin Cancer Res. 2021 Aug 24;40(1):264. doi: 10.1186/s13046-021-02065-8.


DOI:10.1186/s13046-021-02065-8
PMID:34429144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8383365/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/8383365/fc2c8c754e32/13046_2021_2065_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/8383365/ec6465b4e4bd/13046_2021_2065_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/8383365/fc2c8c754e32/13046_2021_2065_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/8383365/ec6465b4e4bd/13046_2021_2065_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/8383365/fc2c8c754e32/13046_2021_2065_Fig2_HTML.jpg

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引用本文的文献

[1]
Metabolic cell death in cancer: mechanisms and therapeutic potential.

Apoptosis. 2025-9-9

[2]
Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice.

Nat Commun. 2025-8-30

[3]
Research and development prospects of TRIM65.

J Cancer Res Clin Oncol. 2025-8-22

[4]
Sirtuin 3 in diabetic kidney disease: mechanisms and pharmacotherapy.

Ren Fail. 2025-12

[5]
Integrating single-cell and bulk RNA sequencing data to construct a pyroptosis-related prognostic signature and analyze the tumor microenvironment in gastric cancer.

Transl Cancer Res. 2025-7-30

[6]
Caerin 1.1/1.9 interfere KHDRBS1-DDX5 regulatory axis to induce IL-18 mediated pyroptosis in a HeLa cell tumour model.

Sci Rep. 2025-7-30

[7]
Amniotic mesenchymal stem cells attenuate diabetic cardiomyopathy by inhibiting pyroptosis via modulation of the TLR4/NF-κb/NLRP3 pathway.

Front Cell Dev Biol. 2025-7-10

[8]
MT1JP/miR-103a-3p induce pyroptosis and regulate the tumor immune microenvironment in gastric cancer.

Sci Rep. 2025-7-23

[9]
Phosphorylated IRF3 promotes GSDME-mediated pyroptosis through RIPK1/FADD/caspase-8 complex formation during mitotic arrest in ovarian cancer.

Cell Commun Signal. 2025-7-1

[10]
Identification of pyroptosis related genes and subtypes in atherosclerosis using multiomic and single cell analysis.

Sci Rep. 2025-7-1

本文引用的文献

[1]
Pyroptosis: a new paradigm of cell death for fighting against cancer.

J Exp Clin Cancer Res. 2021-5-3

[2]
Pyroptosis: mechanisms and diseases.

Signal Transduct Target Ther. 2021-3-29

[3]
Biological Functions of Gasdermins in Cancer: From Molecular Mechanisms to Therapeutic Potential.

Front Cell Dev Biol. 2021-2-9

[4]
Detection of immunogenic cell death and its relevance for cancer therapy.

Cell Death Dis. 2020-11-26

[5]
Caspase-8-dependent gasdermin D cleavage promotes antimicrobial defense but confers susceptibility to TNF-induced lethality.

Sci Adv. 2020-11

[6]
HMGB1 released from GSDME-mediated pyroptotic epithelial cells participates in the tumorigenesis of colitis-associated colorectal cancer through the ERK1/2 pathway.

J Hematol Oncol. 2020-11-7

[7]
Emerging insights on the role of gasdermins in infection and inflammatory diseases.

Clin Transl Immunology. 2020-10-4

[8]
PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.

Nat Cell Biol. 2020-9-14

[9]
Inflammasome Sensor NLRP1 Confers Acquired Drug Resistance to Temozolomide in Human Melanoma.

Cancers (Basel). 2020-9-4

[10]
Ferroptosis, necroptosis, and pyroptosis in anticancer immunity.

J Hematol Oncol. 2020-8-10

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