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
不可逆电穿孔联合瘤内植物病毒免疫治疗在胰腺癌转移模型中诱导全身免疫
英文原题：Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.
查看英文原题
Irreversible electroporation with intratumoral plant virus immunotherapy induces systemic immunity in a metastatic model of pancreatic cancer.
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中文摘要
胰腺癌仍对免疫治疗高度耐药，因此亟需创新策略。本研究探索不可逆电穿孔（IRE）联合植物病毒纳米颗粒，以增强胰腺导管腺癌（PDAC）的免疫应答。IRE是一种已用于临床的非热肿瘤消融技术，但常无法预防转移。豇豆花叶病毒（CPMV）等植物病毒纳米颗粒在多种癌症模型中显示出强免疫刺激作用。我们在具有免疫功能的原位PDAC小鼠模型（伴肝转移）中评估IRE联合瘤内注射CPMV的效果。联合治疗较任一单独治疗显著改善生存，并增加活化、增殖中的CD8+ T细胞浸润。值得注意的是，治疗小鼠的肝转移灶中CD8+ T细胞和NK细胞浸润也增多。此外，淋巴结分析显示树突状细胞成熟增强，CD8+效应记忆T细胞扩增。结果提示IRE与CPMV产生协同作用，可诱发强效局部和全身抗肿瘤免疫。该联合策略可有效将免疫“冷”肿瘤转变为“热”肿瘤，为PDAC患者提供了一种具有临床转化可行性的有前景方法。
展开英文摘要原文
Pancreatic cancer remains highly resistant to immunotherapy, necessitating innovative strategies.
This study explores a novel combination of irreversible electroporation (IRE) and plant virus-based nanoparticles to enhance immune responses in pancreatic ductal adenocarcinoma (PDAC). IRE is a non-thermal tumor ablation technique already in clinical use, but it often fails to prevent metastasis.
Plant viral nanoparticles, such as cowpea mosaic virus (CPMV), have shown potent immune-stimulating properties in various cancer models. Using an immunocompetent orthotopic PDAC mouse model with liver metastases, we evaluated the impact of combining IRE and intratumoral CPMV. Combination therapy significantly improved survival and increased infiltration of activated, profilerating CD8 + T cells compared to either treatment alone.
Notably, liver metastases from treated mice also showed elevated CD8 + T and NK cell infiltration.
Further, lymph node analysis revealed enhanced dendritic cell maturation and expansion of CD8 + effector memory T cells. These results suggest that IRE and CPMV synergize to generate robust local and systemic anti-tumor immunity. This combinatorial strategy effectively converts immunologically "cold" tumors into "hot" tumors, offering a promising approach that can be feasibly translated to PDAC patients.
论文信息
- 作者
- Ledezma DK、Joshi U、Nguyen-Ta K、Sonowal H、Russo H、Newton IG、Steinmetz NF、White RR
- 第一作者单位
- Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA; Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, CA, USA; Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA, USA.United States
- 通讯作者单位
- Moores Cancer Center, University of California San Diego, La Jolla, CA, USA; Department of Surgery, University of California San Diego, La Jolla, CA, USA. Electronic address: rewhite@health.ucsd.edu.United States
- 期刊
- Cancer letters2025 Dec 1
- 原文标识
- PubMed 41045984 · DOI 10.1016/j.canlet.2025.218074
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