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:Natural killer cell therapies in cancer: innovations, challenges, and future directions.
Natural killer cell therapies in cancer: innovations, challenges, and future directions.
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基于 NK 细胞的疗法是癌症免疫治疗中一条有前景的途径,但需要精心设计的解决方案来克服其固有局限性。生物标志物指导的患者选择、与现有治疗模式的整合以及国际合作方面的进展,对于将 NK 细胞生物学转化为有效且持久的临床结局至关重要。
自然杀伤(NK)细胞是先天免疫效应细胞,无需预先致敏即可清除恶性细胞。通过识别细胞应激信号并释放炎症介质,它们参与免疫监视和免疫调节。其治疗潜力在于能够跨越供者屏障发挥作用,且移植物相关并发症风险较低;然而,由于肿瘤免疫逃逸以及在抑制性环境中持久性有限,临床转化仍面临挑战。涵盖领域:本综述总结了NK细胞在肿瘤免疫中的生物学作用,并探讨了近期利用其细胞毒性和调节特性的治疗策略。我们讨论了临床应用的障碍,包括免疫抑制、抗原丢失和生产限制。此外,我们重点介绍了旨在提高治疗疗效的新兴策略,如基因编辑、合理的联合治疗和标准化临床试验设计。
INTRODUCTION: Natural killer (NK) cells are innate immune effectors that can eliminate malignant cells without prior sensitization. By recognizing cellular stress signals and releasing inflammatory mediators, they contribute to immune surveillance and regulation.
Their therapeutic potential lies in their ability to act across donor barriers with a reduced risk of graft-related complications; however, clinical translation remains challenging due to tumor immune evasion and limited persistence in suppressive environments. AREAS COVERED: This review summarizes the biological roles of NK cells in cancer immunity and examines recent therapeutic approaches that harness their cytotoxic and regulatory properties.
We discuss barriers to clinical application, including immune suppression, antigen loss, and manufacturing limitations.
In addition, we highlight emerging strategies, such as gene editing, rational combination therapies, and standardized clinical trial designs, aimed at improving therapeutic efficacy. EXPERT OPINION: NK cell-based therapies represent a promising avenue in cancer immunotherapy but require carefully designed solutions to overcome their inherent limitations.
Advances in biomarker-guided patient selection, integration with existing treatment modalities, and international collaboration will be critical for translating NK cell biology into effective and durable clinical outcomes.
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