细胞焦亡在炎症和抗肿瘤免疫中的分子机制和功能。
Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity.
机构信息
Xiangya Cancer Center, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Road 87, Changsha 410008, Hunan, China; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China; Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.
出版信息
Mol Cell. 2021 Nov 18;81(22):4579-4590. doi: 10.1016/j.molcel.2021.09.003. Epub 2021 Sep 24.
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.
规范地说，半胱天冬酶-1 通过炎症小体信号通路对gasdermin D (GSDMD) 的切割触发了免疫细胞焦亡（ICP），作为宿主防御病原体感染的一种方式。然而，最近发现癌细胞焦亡（CCP）是通过不同的分子机制激活的，其中执行者是 GSDMB、GSDMC 和 GSDME，而不是 GSDMD。此外，gasdermin 蛋白的切割诱导 CCP 需要凋亡半胱天冬酶和颗粒酶，而不是炎性半胱天冬酶。蛋白酶切割的 gasdermin 蛋白的充分积累是 CCP 的前提。ICP 或 CCP 引起的炎症会导致抗肿瘤免疫产生截然相反的影响，因为持续时间和释放的细胞内容物不同，从而对治疗结果产生相反的影响。在这里，我们专注于 ICP 和 CCP 的不同机制，并讨论 ICP 和 CCP 在炎症和抗肿瘤免疫中的作用，这些作用代表了可操作的靶点。
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