Pyroptosis

Pyroptosis is a lytic, strongly inflammatory form of regulated cell death, named from the Greek roots for “fire” and “falling.” It is executed by the gasdermin family of pore-forming proteins: once a gasdermin is proteolytically cleaved by an inflammatory caspase (in the canonical or non-canonical inflammasome pathways), an executioner caspase, or a granzyme, its liberated pore-forming domain inserts into the plasma membrane, causing cell swelling, lysis, and release of pro-inflammatory cytokines such as IL-1β and IL-18. In cancer, tumors frequently silence gasdermin genes (e.g., by promoter hypermethylation of GSDME) to evade this immunostimulatory death pathway.