Enhancing Gasdermin-induced tumor pyroptosis through preventing ESCRT-dependent cell membrane repair augments antitumor immune response.

ABSTRACT: Pore-forming Gasdermin protein-induced pyroptosis in tumor cells promotes anti-tumor immune response through the release of pro-inflammatory cytokines and immunogenic substances after cell rupture. However, endosomal sorting complexes required for transport (ESCRT) III-mediated cell membrane repair significantly diminishes the tumor cell pyroptosis by repairing and subsequently removing gasdermin pores. Here, we show that blocking calcium influx-triggered ESCRT III-dependent membrane repair through a biodegradable nanoparticle-mediated sustained release of calcium chelator (EI-NP) strongly enhances the intracellularly delivered GSDMD-induced tumor pyroptosis via a bacteria-based delivery system (VNP-GD). An injectable hydrogel and a lyophilized hydrogel-based cell patch are developed for p

SUBMITTER: Li Z 

PROVIDER: S-EPMC9592600 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature