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 therapy in hepatocellular carcinoma: a comprehensive review.
Natural killer cell therapy in hepatocellular carcinoma: a comprehensive review.
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肝细胞癌仍然是全球主要的医疗负担,预计到2040年将导致130万人死亡。大多数HCC患者确诊时已处于晚期,导致预后不良。开发靶向免疫疗法对于应对这一未满足的临床挑战至关重要。自然杀伤(NK)细胞已成为治疗实体瘤的一种有前景的细胞治疗方法。NK细胞具有独特的识别和摧毁癌细胞的能力,且无需预先致敏。
在此,我们全面讨论了NK细胞治疗的潜在方法、开发策略和当前面临的挑战。此外,还讨论了免疫治疗的进展,包括过继性NK细胞疗法,以及增强NK细胞抗HCC功能的策略,如基于细胞因子的治疗、免疫检查点抑制剂、基于疫苗的方法、基因递送、非编码RNA、基于抗体的方法和天然药物。这项综合性研究通过整合近期关于NK细胞对HCC差异性影响的研究发现,提供了独特的视角。
我们重点介绍了NK细胞工程和免疫检查点调控的最新进展,并对治疗策略进行了比较分析。此外,我们批判性地评估了基于NK细胞疗法的转化挑战,特别聚焦于其有限的体内持久性和肿瘤免疫逃逸策略。
Hepatocellular carcinoma remains a major healthcare burden worldwide and is predicted to be the cause of death of 1. 3 million people in 2040. Most HCC patients are diagnosed in advanced stages, leading to a poor prognosis. The development of targeted immunotherapies is essential to address this unmet clinical challenge. Natural killer (NK) cells have emerged as a promising cell-based therapeutic approach for treating solid tumors. NK cells have the distinctive ability to identify and destroy cancer cells without requiring prior sensitization.
Here, we discuss potential approaches, developing strategies, and current challenges of NK cell therapy reported completely.
In addition, advancements in immunotherapy, including adoptive NK cell therapy, and the strategies to boost NK cell function against HCC such as cytokine-based treatments, immune checkpoint inhibitors, vaccine-based approaches, genetic delivery, non-coding RNAs, antibody-based methods, and natural agents have been discussed. This comprehensive study provides a unique perspective by integrating recent findings on the differential impact of NK cells on HCC.
We highlight the latest advances in NK cell engineering and immune checkpoint modulation, presenting a comparative analysis of therapeutic strategies.
Furthermore, we critically assess the translational challenges associated with NK cell-based therapies, particularly focusing on their limited in vivo persistence and tumor immune evasion strategies.
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