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-based immunotherapies for colorectal cancer: Current strategies, challenges, and future perspectives.
Natural killer cell-based immunotherapies for colorectal cancer: Current strategies, challenges, and future perspectives.
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自然杀伤(NK)细胞可在无需预先致敏的情况下识别并清除肿瘤细胞,因此已成为治疗结直肠癌的有前景药物。本综述全面考察NK细胞免疫治疗方法,包括细胞因子治疗、免疫检查点抑制、抗体依赖的细胞毒作用和过继细胞转移,并突出其各自的临床潜力与局限。我们讨论NK细胞扩增、基因工程(尤其是嵌合抗原受体-NK开发)及肿瘤微环境介导免疫抑制等关键挑战。此外,还探讨旨在克服当前障碍的创新策略,如联合治疗、纳米技术增强递送和个体化医疗。本综述最后展望未来方向,强调需要标准化生产流程、开发提高NK细胞持久性的新策略,并对新兴技术进行临床验证,从而使NK细胞免疫疗法成为结直肠癌治疗的变革性手段。
Natural killer (NK) cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization. In this review, NK cell-based immunotherapeutic approaches, including cytokine therapy, immune checkpoint inhibition, antibody-dependent cellular cytotoxicity, and adoptive cell transfer, are comprehensively examined, and their respective clinical potential and limitations are highlighted.
We discuss critical challenges in NK cell expansion, genetic engineering (particularly chimeric antigen receptor-NK development), and tumor microenvironment-mediated immunosuppression.
Furthermore, we explore innovative strategies such as combination therapies, nanotechnology-enhanced delivery, and personalized medicine approaches that aim to overcome the current barriers. The review concludes with future directions emphasizing the need for standardized manufacturing protocols, new strategies to improve NK cell persistence, and clinical validation of emerging technologies, positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.
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