CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Igniting hope: Harnessing NLRP3 inflammasome-GSDMD-mediated pyroptosis for cancer immunotherapy.
Igniting hope: Harnessing NLRP3 inflammasome-GSDMD-mediated pyroptosis for cancer immunotherapy.
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在当代肿瘤学领域,以免疫检查点阻断(ICB)疗法为代表的免疫治疗,已成为癌症治疗中创新的灯塔。尽管前景广阔,但该疗法的进展仍受限于临床缓解率不理想。为应对这一挑战,调控NLRP3炎症小体-GSDMD介导的细胞焦亡通路有望成为增强免疫治疗疗效的手段。在该通路中,NLRP3炎症小体作为关键的分子传感器,响应机体内炎症刺激。其激活通过切割GSDMD导致细胞因子白细胞介素1和白细胞介素18的释放,从而形成膜孔并可能导致细胞焦亡。这一系列过程对肿瘤的发生发展产生深远影响,其功能和表达在不同肿瘤类型和发育阶段表现出差异性。
因此,理解NLRP3炎症小体和GSDMD介导的细胞焦亡在不同肿瘤中的具体作用,对于理解肿瘤发生及制定精准治疗策略至关重要。本综述旨在阐明NLRP3炎症小体的结构和激活机制,以及GSDMD介导的细胞焦亡的诱导机制。
此外,我们全面概述了该通路在多种癌症类型中的参与及其在肿瘤免疫治疗、纳米治疗和其他领域的应用。重点在于利用这一方法在免疫治疗领域增强ICB疗法的可行性。
此外,我们还讨论了该通路在其他免疫治疗方法中的潜在应用,如CAR-T 细胞疗法和肿瘤疫苗。
In the contemporary landscape of oncology, immunotherapy, represented by immune checkpoint blockade (ICB) therapy, stands out as a beacon of innovation in cancer treatment. Despite its promise, the therapy's progression is hindered by suboptimal clinical response rates. Addressing this challenge, the modulation of the NLRP3 inflammasome-GSDMD-mediated pyroptosis pathway holds promise as a means to augment the efficacy of immunotherapy. In the pathway, the NLRP3 inflammasome serves as a pivotal molecular sensor that responds to inflammatory stimuli within the organism.
Its activation leads to the release of cytokines interleukin 1 and interleukin 18 through the cleavage of GSDMD, thereby forming membrane pores and potentially resulting in pyroptosis. This cascade of processes exerts a profound impact on tumor development and progression, with its function and expression exhibiting variability across different tumor types and developmental stages.
Consequently, understanding the specific roles of the NLRP3 inflammasome and GSDMD-mediated pyroptosis in diverse tumors is imperative for comprehending tumorigenesis and crafting precise therapeutic strategies. This review aims to elucidate the structure and activation mechanisms of the NLRP3 inflammasome, as well as the induction mechanisms of GSDMD-mediated pyroptosis.
Additionally, we provide a comprehensive overview of the involvement of this pathway in various cancer types and its applications in tumor immunotherapy, nanotherapy, and other fields. Emphasis is placed on the feasibility of leveraging this approach to enhance ICB therapy within the field of immunotherapy.
Furthermore, we discuss the potential applications of this pathway in other immunotherapy methods, such as chimeric antigen receptor T-cell (CAR-T) therapy and tumor vaccines.
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