【摘要】 头颈部鳞状细胞癌（head and neck squamous cell carcinoma,HNSCC）与肿瘤微环境（tumor microenvironment,TME）中NLRP3炎症小体介导的慢性炎症密切相关。NLR家族Pyrin域蛋白3(NLRP3)通过整合病原及应激信号，动态调控IL-1β/IL-18分泌及细胞焦亡；表现出功能的双重性，既可激活Caspase-1/GSDMD通路诱导肿瘤焦亡发挥抑癌作用，亦通过重塑免疫抑制性TME（驱动M2型巨噬细胞极化、抑制NETs相关焦亡、促进肿瘤干细胞维持及化疗耐药）驱动恶性进展。临床前研究表明，小分子抑制剂（MCC950、BAY11-7 082）、天然药物假马齿苋提取物以及IL-1信号通路生物制剂等靶向NLRP3的干预策略能显著抑制HNSCC以及其他肿瘤的生长和转移。本文系统解析NLRP3动态网络，评估靶向治疗的转化潜力，旨在为突破HNSCC治疗瓶颈提供新方向。更多还原

【Abstract】 Head and neck squamous cell carcinoma(HNSCC) progression is closely associated with chronic inflammation mediated by the NLRP3 inflammasome within the tumor microenvironment(TME). The NLRP3 inflammasome integrates pathogen-associated and stress-induced signals to dynamically regulate IL-1β/IL-18 secretion and pyroptosis. Through its action, NLRP3 inflammasome exhibits a functional duality, exerting tumor-suppressive effects by activating the Caspase-1/GSDMD pathway to induce tumor cell pyroptosis while also driving malignant progression through remodeling of immunosuppressive TMEs. This remodeling includes driving M2-type macrophage polarization and suppressing NETs-associated pyroptosis, thereby promoting cancer stem cell maintenance and contributing to chemotherapy resistance.Preclinical studies have confirmed that NLRP3-targeted strategies, including small-molecule inhibitors(MCC950 and BAY11-7082), Bacopa monnieri, and IL-1 signaling biologics, significantly suppress tumor growth and metastasis in HNSCC and other cancers. In this review, we systematically decipher the NLRP3 regulatory network, evaluate the translational potential of targeted interventions, and offer novel therapeutic avenues to overcome treatment barriers in HNSCC.更多还原