Canonically, gasdermin D (GSDMD) cleavage by caspase-1 through inflammasome signaling triggers immune cell pyroptosis (ICP) as a host defense against pathogen infection. However, cancer cell pyroptosis (CCP) was recently discovered to be activated by distinct molecular mechanisms in which GSDMB, GSDMC, and GSDME, rather than GSDMD, are the executioners. Moreover, instead of inflammatory caspases, apoptotic caspases and granzymes are required for gasdermin protein cleavage to induce CCP. Sufficient accumulation of protease-cleaved gasdermin proteins is the prerequisite for CCP. Inflammation induced by ICP or CCP results in diametrically opposite effects on antitumor immunity because of the differential duration and released cellular contents, leading to contrary effects on therapeutic outcomes. Here, we focus on the distinct mechanisms of ICP and CCP and discuss the roles of ICP and CCP in inflammation and antitumor immunity, representing actionable targets.

典型地，gasdermin D (GSDMD) 通过炎性体信号被 caspase-1 切割触发免疫细胞焦亡 (ICP) 作为宿主防御病原体感染。然而，最近发现癌细胞焦亡 (CCP) 被不同的分子机制激活，其中 GSDMB、GSDMC 和 GSDME 而不是 GSDMD 是执行者。此外，gasdermin 蛋白裂解诱导 CCP 需要凋亡的半胱天冬酶和颗粒酶，而不是炎症半胱天冬酶。蛋白酶切割的 gasdermin 蛋白的充分积累是 CCP 的先决条件。由 ICP 或 CCP 引起的炎症由于持续时间和释放的细胞内容物不同，导致抗肿瘤免疫力产生截然相反的影响，从而对治疗结果产生相反的影响。这里，