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
脐带血来源的 NK 细胞：在非小细胞肺癌中的体外、体内及临床抗肿瘤活性（病例系列）
英文原题：Umbilical cord blood-derived natural killer cells: in vitro, in vivo, and clinical antitumor activity in non-small cell lung cancer (case series).
查看英文原题
Umbilical cord blood-derived natural killer cells: in vitro, in vivo, and clinical antitumor activity in non-small cell lung cancer (case series).
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研究概要
UCB-NK 细胞有望成为 NSCLC 的替代治疗方法，并有可能与其他疗法联合使用以提高生存率和生活质量。然而，需要大规模临床研究来验证安全性和优化治疗方案。
研究思路结论见上方概要
背景
肺癌仍是全球范围内疾病负担沉重、死亡率高的疾病。尽管当前非小细胞肺癌（NSCLC）的治疗手段——手术、化疗、靶向治疗以及基于免疫检查点抑制剂的免疫治疗——已适度改善了预后，但耐药性和严重副作用限制了疗效，凸显了对替代疗法的迫切需求。
方法
本研究通过体外、体内和临床分析评估了脐带血来源自然杀伤（UCB-NK）细胞在NSCLC中的治疗潜力。在不同效靶比（E:T）下，评估了扩增的UCB-NK细胞对NSCLC细胞系（A549、NCI-H1975）的体外细胞毒性。在荷A549的NCG（NOD-Prkdcem26Cd52Il2rgem26Cd22/Gpt）小鼠中，检查了UCB-NK细胞联合IL-2治疗的体内抗肿瘤疗效。此外，还评估了5例接受多模式治疗联合UCB-NK输注的NSCLC患者的临床病例系列。
结果
体外实验中，扩增的UCB-NK细胞对NSCLC细胞系表现出剂量依赖性细胞毒性，在E:T比例为5:1和10:1时，肿瘤细胞裂解率高达80%。在荷A549的NCG小鼠中，与IL-2单药治疗相比，UCB-NK/IL-2联合治疗使肿瘤体积显著缩小25.59%，肿瘤重量减少26.5%（P < 0.01）。对五例接受多模式治疗联合UCB-NK输注的NSCLC病例进行临床评估，显示疾病稳定。
展开英文摘要原文
BACKGROUND
Lung cancer remains a globally burdensome disease with high mortality. While current non-small cell lung cancer (NSCLC) treatments - surgery, chemotherapy, targeted therapy, and immune checkpoint inhibitor-based immunotherapy - have modestly improved outcomes, drug resistance and severe side effects limit efficacy, highlighting the urgent need for alternative therapies.
MATERIALS AND METHODS
This study assessed the therapeutic potential of umbilical cord blood-derived natural killer (UCB-NK) cells in NSCLC via in vitro, in vivo , and clinical analyses. In vitro cytotoxicity of expanded UCB-NK cells was evaluated against NSCLC cell lines (A549, NCI-H1975) at various effector-to-target (E:T) ratios. In vivo antitumor efficacy was examined in A549-bearing NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/Gpt) mice treated with UCB-NK cells combined with IL-2. Additionally, a clinical case series of five NSCLC patients receiving multimodal therapy plus UCB-NK infusions was evaluated.
RESULTS
In vitro , expanded UCB-NK cells showed dose-dependent cytotoxicity against NSCLC cell lines, achieving up to 80% tumor cell lysis at E:T ratios of 5:1 and 10:1. In A549-bearing NCG mice, UCB-NK/IL-2 combination therapy significantly reduced tumor volume by 25.59% and tumor weight by 26.5% compared to IL-2 monotherapy ( P < 0.01). Clinical evaluation of five NSCLC cases receiving multimodal therapy plus UCB-NK infusions demonstrated disease stabilization.
CONCLUSION
UCB-NK cells hold promise as an alternative therapeutic approach for NSCLC, with the potential to combine with other therapies to improve survival and quality of life. However, large-scale clinical studies are needed to verify safety and optimize treatment protocols.
论文信息
- 作者
- Zhang ZL、Wu Q、Chen J、Zhao ZL、Cheng Z、Jin Y、Wu C、Yang ZY
- 第一作者单位
- The School of Pharmacy, North China University of Science and Technology, Tangshan, China.China
- 通讯作者单位
- NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.China
- 期刊
- Annals of medicine and surgery (2012)2026 Jul
- 原文标识
- PubMed 42433755 · DOI 10.1097/MS9.0000000000005014
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