Pyroptosis at the forefront of anticancer immunity

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.

A Novel Pyroptosis-Related Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Osteosarcoma

“…Pyroptosis, a form of programmed cell death, was found to play a dual role in both promoting and inhibiting the growth of different tumor cells (Loveless et al, 2021). Several recent studies have highlighted the relevance of pyroptosis-related genes as candidate biomarkers for prognosis and therapeutic response in patients with different cancer types (Ju A. et al, 2021;Lin W. et al, 2021;Shao et al, 2021;Ye et al, 2021).…”

Inhibition of HMGB1 Ameliorates the Maternal-Fetal Interface Destruction in Unexplained Recurrent Spontaneous Abortion by Suppressing Pyroptosis Activation

“…Pyroptosis, which has been extensively studied recently, is a lytic and inflammatory programmed cell death pathway different from apoptosis ( 17 ). It is involved in the occurrence and development of a variety of diseases in multiple organs of the body.…”

“…It is involved in the occurrence and development of a variety of diseases in multiple organs of the body. Pyroptosis directly assembles the inflammasome (NLRP3) by damage-associated molecular pattern (DAMP) and activates the cysteine protease caspase-1, allowing the translocation of the N-terminal domain fragment of the GasderminD (GSDMD) protein to the cell membrane to form β-barrel transmembrane pores ( 17 ). Hence, the plasma membranes were rapidly ruptured to release cellular contents and a large number of inflammatory factors, and send proinflammatory signals to adjacent cells to recruit inflammatory cells and induce an inflammatory response, eventually causing cell death ( 18 ).…”

Integrated analysis of expression, prognostic value and immune infiltration of GSDMs in hepatocellular carcinoma

“…All the six GSDMs share a highly conserved pore-forming domain which is responsible for the membrane permeabilization and cell pyroptosis [ 5 – 7 ]. Pyroptosis is a novel form of lytic programmed cell death with the characterization of pro-inflammation that is broadly involved in a variety of biological processes such as human development and immune response [ 8 – 10 ]. Besides, emerging researches have revealed the strong correlation between the dysregulation of GSDMs and the initiation and development of a various type of cancer [ 11 ].…”