Pyroptosis at the forefront of anticancer immunity

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.

Automated summary

Pyroptosis, a lytic and inflammatory programmed cell death pathway, has shown potential in addressing tumor resistance to apoptosis and the immunosuppressive tumor microenvironment by inducing a robust inflammatory response and marked tumor regression. Gasdermin proteins mediate pyroptosis and facilitate immune cell activation and infiltration, but aberrant pyroptosis may also contribute to tumor progression by upregulating gasdermin proteins in certain cancers. Harnessing pyroptosis as a tool in anticancer strategies shows promise in novel interventions.