Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Immunol. 2023 Jan 18;14:1082165. doi: 10.3389/fimmu.2023.1082165. eCollection 2023.
Pyroptosis is a programmed necrotic cell death mediated by pore-forming Gasdermin (GSDM) proteins. After being unleashed from the C-terminal auto-inhibitory domains by proteolytic cleavage, the N-terminal domains of GSDMs oligomerize and perforate on the plasma membrane to induce cytolytic pyroptosis, releasing immune mediators and alarming the immune system. Upon infection or danger signal perception, GSDMD that functions downstream of the inflammasome, a supramolecular complex for inflammatory caspase activation, is cleaved and activated by inflammasome-activated caspase-1/4/5/11 in immune cells and epithelial cells to trigger pyroptosis and exert anti-infection protection. Unlike this inflammasome-activated pyroptosis (IAP), recent studies also suggest an emerging role of cancer-associated pyroptosis (CAP), mediated by other GSDMs in cancer cells, in provoking anti-tumor immunity. IAP and CAP share common features like cell membrane rupture but also differ in occurrence sites, activating mechanisms, secreting cytokines and biological outcomes. Here we review the most recent knowledge of cancer-associated pyroptosis and present a promising avenue for developing therapeutic interventions to enhance anti-tumor immunity for cancer treatment.
细胞焦亡是一种由 Gasdermin (GSDM) 蛋白介导的程序性细胞坏死。在被蛋白酶切割从 C 端自身抑制结构域释放后，GSDM 的 N 端结构域寡聚化并在质膜上穿孔，导致细胞溶解性细胞焦亡，释放免疫介质并引起免疫系统的警觉。在感染或危险信号感知后，作为炎症小体下游发挥作用的 GSDMD（炎症小体是一种用于炎症性半胱天冬酶激活的超分子复合物），在免疫细胞和上皮细胞中被炎症小体激活的半胱天冬酶-1/4/5/11 切割和激活，从而引发细胞焦亡并发挥抗感染保护作用。与这种炎症小体激活的细胞焦亡（IAP）不同，最近的研究还表明，在癌细胞中，由其他 GSDM 介导的癌症相关细胞焦亡（CAP）在引发抗肿瘤免疫方面也具有重要作用。IAP 和 CAP 具有细胞膜破裂等共同特征，但在发生部位、激活机制、分泌细胞因子和生物学结果等方面存在差异。本文综述了癌症相关细胞焦亡的最新知识，并提出了一种有前途的治疗干预途径，以增强抗肿瘤免疫，用于癌症治疗。
