Figure 6.

Other pathways of GSDMDs-dependent pyroptosis. In the granzyme-mediated pathway, GzmA secreted from NK cells and CD8+ T cells induces GSDMB-mediated pyroptosis. CAR-T cells can release a great deal of perforin and GzmB activating caspase-3,which cause GSDME cleaved by caspase-3 in target cells.Chemotherapeutic drugs could induce caspase-3-mediated GSDME cleavage with high GSDME expression and form GSDME-NT, causing pyroptosis of tumor cells. The inhibition of TAK1 and IKK activates caspase-8 via the lysosomal rag-ragulator complex, resulting in GSDMD cleavage and pyroptosis by Yersinia. Under hypoxia conditions, p-Stat3 interacts with PD-L1 and upregulates the transcription of GSDMC. Activated by TNF-α, caspase-8 cleaves GSDMC into GSDMC-NT, resulting in pyroptosis. Group A Streptococcal (GAS) cysteine protease SpeB cleaves directly to induce GSDMA-dependent pyroptosis.