GSDME and neoplasm: In 2020, Liu et al. demonstrated that chimeric antigen receptor (CAR) T-cells can quickly engage caspase-3 in target cells through granzyme B release, triggering the caspase-3/GSDME pyroptosis pathway and leading to widespread pyroptotic cell death.37 In addition, granzyme B directly fragments GSDME to stimulate pyroptosis, enhance anti-tumor immunity, and restrict tumor expansion.26 Natural killer and cytotoxic T cells have been observed to eliminate GSDMB+ cells via pyroptosis, with cytotoxicity resulting from granzyme A (GzmA)-mediated GSDMB fragmentation at Lys229/Lys244.