Pyroptosis: A New Strategy for Oncolytic Virus Therapy of Cancer

Abstract

In recent years, pyroptosis, as a form of proinflammatory programmed death, has been found to play a key role in the anti-tumor mechanism of OVs. This article systematically reviews the molecular mechanism of pyroptosis and tumor immune regulation, summarizes novel therapeutic strategies such as genetic engineering of OVs to enhance pyroptosis and combined with immune checkpoint inhibitors (ICIs), and analyzes their effects on tumor microenvironment (TME) immune remodeling. The results showed that OVs mainly induced pyroptosis by activating the caspase-3/GSDME pathway, releasing inflammatory factors (such as IL-18, HMGB1) and damage-associated molecular patterns (DAMPs), recruiting CD8+ T cells and natural killer (NK) cell infiltration, and thus transforming "cold tumors" into "hot tumors". OVs can be transformed to express GSDM proteins, regulate mitochondrial dysfunction, and target tumor immune components to promote the treatment of tumors through pyroptosis. This article provides a theoretical basis for the clinical transformation of OVs and suggests that pyroptosis-based combination therapy may become an important direction for future tumor im-munotherapy.