细胞焦亡调控泌尿系肿瘤免疫微环境的机制及治疗转化

Mechanism and therapeutic transformation of pyroptosis in regulating immune microenvironment of urological tumors

  • 摘要: 细胞焦亡是一种程序性细胞死亡方式,有别于经典的细胞凋亡与被动性细胞坏死。细胞焦亡在激活固有免疫应答、驱动局部炎症反应、调控免疫细胞活化与浸润,以及重塑肿瘤免疫微环境等方面发挥关键作用。近年来,细胞焦亡在泌尿系统肿瘤发生、发展及治疗响应中的作用日益受到关注。现有研究表明,细胞焦亡在多种肿瘤中呈现双重调控效应: 一方面可通过诱导肿瘤细胞裂解性死亡而发挥抗肿瘤作用; 另一方面,在特定微环境条件下,其介导的慢性炎症反应可能促进免疫逃逸,进而推动肿瘤进展。本文系统综述了细胞焦亡在肾细胞癌、膀胱癌和前列腺癌三大常见泌尿系统肿瘤中的分子机制异同,总结其在肿瘤发生发展过程中的调控网络及潜在治疗靶点,并阐述通过调控细胞焦亡通路以增强免疫检查点抑制剂疗效的相关研究进展,旨在为泌尿系统肿瘤的精准治疗提供新策略与理论依据。

     

    Abstract: Pyroptosis is a form of programmed cell death that differs from classical apoptosis and passive necrosis. It plays a crucial role in activating innate immune responses, driving local inflammatory reactions, regulating immune cell activation and infiltration, and remodeling the tumor immune microenvironment. In recent years, the role of pyroptosis in the initiation, progression, and treatment response of urological tumors has garnered increasing attention. Current studies have demonstrated that pyroptosis exhibits dual regulatory effects in various tumors: on the one hand, it exerts anti-tumor effects by inducing lytic death of tumor cells; on the other hand, under specific microenvironmental conditions, the chronic inflammatory response mediated by pyroptosis may promote immune escape, thereby driving tumor progression. This review systematically summarized the similarities and differences in the molecular mechanisms of pyroptosis in three common urological tumors, namely renal cell carcinoma, bladder cancer, and prostate cancer. It also summarized the regulatory networks and potential therapeutic targets during tumor initiation and progression. Furthermore, it elucidated the research progress on enhancing the efficacy of immune checkpoint inhibitors by modulating pyroptosis pathways, aiming to provide novel strategies and theoretical foundations for the precise treatment of urological.

     

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