Pyroptosis: A road to next-generation cancer immunotherapy

The goal of cancer immunotherapy is to clear tumor cells by activating antitumor immunity, especially by mobilizing tumor-reactive CD8⁺T cells. Pyroptosis, programmed lytic cell death mediated by gasdermin (GSDM), results in the release of cellular antigens, damage-associated molecular patterns (DAMPs) and cytokines. Therefore, pyroptotic tumor cell-derived tumor antigens and DAMPs not only reverse immunosuppression of the tumor microenvironment (TME) but also enhance tumor antigen presentation by dendritic cells, leading to robust antitumor immunity. Exploring nanoparticles and other approaches to spatiotemporally control tumor pyroptosis by regulating gasdermin expression and activation is promising for next-generation immunotherapy.