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
使用 LA-PegPI 聚合物基因疫苗联合 PD-1 抑制在黑色素瘤中协同激活抗肿瘤免疫
英文原题：Synergistic antitumor immune activation in melanoma using LA-PegPI polymeric gene vaccine in conjunction with PD-1 inhibition.
查看英文原题
Synergistic antitumor immune activation in melanoma using LA-PegPI polymeric gene vaccine in conjunction with PD-1 inhibition.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
癌症基因疫苗联合免疫检查点抑制剂在黑色素瘤治疗中具有前景，但递送载体仍然至关重要。在此，我们报道了LA-PegPI，一种半乳糖修饰的聚合物载体，可将质粒DNA特异性递送至树突状细胞（DCs），实现比商业试剂更高的转染效率且细胞毒性低。LA-PegPI/pDNA复合物激活TLR4/NF-κB和NLRP3/caspase-1通路，诱导DC成熟并分泌IL-6、TNF-α、IL-1β和IL-12。在B16-OVA黑色素瘤模型中，LA-PegPI/pOVA疫苗接种与anti-PD-1协同抑制肿瘤生长、减少肺转移并延长生存期，同时伴随CD8 + T细胞、NK细胞和Th1细胞因子增加。该聚合物平台整合了靶向递送和内在佐剂活性，为增强检查点免疫治疗提供了一种安全策略。
展开英文摘要原文
Cancer gene vaccines combined with immune checkpoint inhibitors hold promise for melanoma therapy, but delivery vehicles remain critical.
Here, we report LA-PegPI, a galactose-modified polymeric vector that delivers plasmid DNA specifically to dendritic cells (DCs), achieving higher transfection efficiency than commercial reagents with low cytotoxicity. LA-PegPI/pDNA complexes activate TLR4/NF-κB and NLRP3/caspase-1 pathways, inducing DC maturation and secretion of IL-6, TNF-α, IL-1β, and IL-12.
In B16-OVA melanoma models, LA-PegPI/pOVA vaccination synergizes with anti-PD-1 to suppress tumor growth, reduce lung metastasis, and prolong survival, accompanied by increased CD8 + T, NK cells, and Th1 cytokines. This polymer platform integrates targeted delivery and intrinsic adjuvanticity, offering a safe strategy to enhance checkpoint immunotherapy.
论文信息
- 作者
- Li W、Liu L、Yao X、Abi ME、Ge C、Bian D、Ding X、Pang X
- 单位
- Cancer Biotherapy Center & Cancer Research Institute, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, China.China
- 期刊
- iScience2026 Sep 18
- 原文标识
- PubMed 42699759 · DOI 10.1016/j.isci.2026.117177
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →