CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives.
Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives.
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细胞焦亡是一种独特的程序性细胞死亡形式,其特征为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,特别关注炎症小体激活和gasdermin家族蛋白(GSDMs)。文章审视了焦亡性细胞死亡在重塑肿瘤免疫微环境(TIME)中的作用,涉及肿瘤细胞和免疫细胞,并讨论了通过小分子调节剂、工程化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焦亡通路的最新进展。我们还回顾了靶向细胞焦亡以增强肿瘤免疫治疗(包括免疫检查点抑制剂、过继细胞疗法和肿瘤疫苗)的最新进展和未来方向。本研究表明,靶向细胞焦亡为放大抗肿瘤免疫反应和克服现有免疫治疗耐药性提供了一条有前景的途径,有望带来更有效的癌症治疗。
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.
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