RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Update of NK cell therapy in pediatric brain tumors.
Update of NK cell therapy in pediatric brain tumors.
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新一代工程化 NK 细胞的开发如今为脑肿瘤治疗开启了一个充满治疗乐观的新时代。
**引言:**儿童脑肿瘤是癌症相关死亡的首要原因。尽管多种治疗方式已有进展,此类恶性肿瘤的总生存率仍较差。免疫疗法作为新的治疗范式受到关注,但血脑屏障(BBB)、低突变负荷和免疫抑制性微环境限制了临床疗效。 **目的:**本文主要回顾NK细胞病理生理学及推动其转化为儿童脑肿瘤临床试验的临床前研究,并概述重编程NK细胞、增强其持久性和向肿瘤部位归巢,以及缓解肿瘤微环境(TME)抑制作用的策略。 **结果:**NK细胞疗法在儿童脑肿瘤中的应用日益受到关注,因为其固有的肿瘤杀伤机制无需预先致敏,也不依赖MHC抗原识别。相较自体NK细胞,现货型来源通常更受青睐,原因是成本较低、生产时间较短、患者获得速度更快。改进的体外扩增方法和创新的多重工程化策略可制备效能更高的NK细胞,赋予其强效肿瘤特异性细胞毒作用、更长体内持续性及抵抗TME障碍的能力。 **结论:**新一代工程化NK细胞的开发为脑肿瘤治疗带来了新的乐观前景。目前正持续推进临床试验,以评估这些新疗法的安全性和疗效。
The primary objective of this article is to review NK cell pathophysiology and the preclinical studies that have led to its translation into clinical trials for pediatric brain tumors (PBTs). An overview of strategies to reprogram NK cells, enhance their persistence and homing to tumor sites, and mitigate the tumor microenvironment (TME) will be presented.
Use of NK cell therapy is now gaining momentum in PBTs due to its inherent tumor-killing mechanisms, which preclude the need for prior sensitization and MHC-dependent antigen recognition. Off-the-shelf sources of NK cells are often favored due to their lower cost, shorter manufacturing time, and quicker access to patients than autologous cells. Improved methods of ex vivo expansion and innovative multiplexed engineering approaches enable delivery of more efficient NK cells, empowered with robust tumor-specific cytotoxicity, longer in vivo persistence and resistance to the impediments of the TME.
The development of newer generations of engineered NK cells now ushers in an era of therapeutic optimism for the treatment of brain tumors. Efforts are ongoing to deliver safe and efficacious clinical trials using these novel therapeutics.
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