'Gasdermin-mediated pyroptosis: from antibacterial to antitumor immunity' - Lecture

Dr. Feng Shao is known worldwide as a top scientist in the field of pyroptosis research. He will talk about Gasdermina, pore-forming proteins.

Gasdermina are pore-forming proteins conserved from humans to bacteria and execute pyroptosis to stimulate immune responses. GSDMD is cleaved/activated by canonical inflammasome-stimulated caspase-1 and cytosolic LPS-ligated caspase-4/5/11.

I will present the finding that LPS-activated caspase-4/5, but not mouse caspase-11, processes IL-18 in vitro and during bacterial infections, which mainly operates in epithelial cells. LPS-activated caspase-4/11, when occurring in brain endothelial cells, mediates BBB breakdown in response to circulating LPS or during LPS-induced sepsis.

Lastly, I will discuss the role of pyroptosis in stimulating antitumor immunity. Specifically, cytotoxic lymphocytes kill GSDMB-positive cells through pyroptosis, mediated by granzyme A cleavage of GSDMB. IFN-g upregulates GSDMB and promotes pyroptosis of cancer cells including that by CAR-T/TCR-T cells.