Huang Chen, Li Jiayi, Wu Ruiyan, Li Yangqian, Zhang Chenliang
Department of Biotherapy, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Mol Cancer. 2025 May 3;24(1):131. doi: 10.1186/s12943-025-02344-4.
Pyroptosis is a distinct form of programmed cell death characterized by the rupture of the cell membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects the tumor microenvironment and antitumor immunity by releasing damage-associated molecular patterns (DAMPs) and pro-inflammatory mediators, thereby establishing it as a pivotal target in cancer immunotherapy. This review thoroughly explores the molecular mechanisms underlying pyroptosis, with a particular focus on inflammasome activation and the gasdermin family of proteins (GSDMs). It examines the role of pyroptotic cell death in reshaping the tumor immune microenvironment (TIME) involving both tumor and immune cells, and discusses recent advancements in targeting pyroptotic pathways through therapeutic strategies such as small molecule modulators, engineered nanocarriers, and combinatory treatments with immune checkpoint inhibitors. We also review recent advances and future directions in targeting pyroptosis to enhance tumor immunotherapy with immune checkpoint inhibitors, adoptive cell therapy, and tumor vaccines. This study suggested that targeting pyroptosis offers a promising avenue to amplify antitumor immune responses and surmount resistance to existing immunotherapies, potentially leading to more efficacious cancer treatments.
细胞焦亡是一种独特的程序性细胞死亡形式，其特征在于细胞膜破裂和强烈的炎症反应。越来越多的证据表明，细胞焦亡通过释放损伤相关分子模式（DAMPs）和促炎介质，显著影响肿瘤微环境和抗肿瘤免疫，从而使其成为癌症免疫治疗的关键靶点。本综述深入探讨了细胞焦亡的分子机制，特别关注炎性小体激活和gasdermin蛋白家族（GSDMs）。它研究了细胞焦亡性细胞死亡在重塑涉及肿瘤细胞和免疫细胞的肿瘤免疫微环境（TIME）中的作用，并讨论了通过小分子调节剂、工程纳米载体以及与免疫检查点抑制剂联合治疗等治疗策略靶向细胞焦亡途径的最新进展。我们还综述了靶向细胞焦亡以增强免疫检查点抑制剂、过继性细胞疗法和肿瘤疫苗的肿瘤免疫治疗的最新进展和未来方向。这项研究表明，靶向细胞焦亡为放大抗肿瘤免疫反应和克服对现有免疫疗法的抗性提供了一条有前景的途径，有可能带来更有效的癌症治疗方法。
