Top and bottom left-hand panels: Killer lymphocytes, such as Natural Killer (NK) cells, secrete perforin and granzyme B to the target cancer cell. Granzyme B enters the cancer cell and cleaves gasdermin E (GSDME) after the site D270, or caspase-3. Active caspase-3 can also cleave GSDME after D270. Cleavage of GSDME liberates its functional N-terminal fragment (N-terminal). The N-terminal fragment of GSDME forms pores on the plasma membrane, resulting in pyroptosis of the cancer cell. Top and bottom right-hand panels: Drug conjugates can be used to promote pyroptosis in cancer cells. Nanoparticle-gasdermin A3 (NP-GSDMA3) and the compound phenylalanine trifluoroborate (Phe-BF3) can enter the cancer cell, whereby Phe-BF3 specifically desilylates NP-GSDMA3 and promotes the release of active GSDMA3 (N-terminal), leading to pyroptosis of the cancer cell. Pyroptosis of cancer cells further triggers the recruitment of immune cells, including macrophages, CD4+ T cells, CD8+ T cells and NK cells, to induce anti-tumor immunity. This recruitment event might depend on the proinflammatory cytokines IL-1β and/or IL-18, and/or inflammatory danger signal/s, but the precise signal/s are unknown (indicated by the question mark).
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