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
肿瘤靶向性溶瘤 HSV-SUR15 增强胶质母细胞瘤的抗肿瘤免疫
英文原题：Tumor-targeting oncolytic HSV-SUR15 enhances anti-tumor immunity in glioblastoma.
查看英文原题
Tumor-targeting oncolytic HSV-SUR15 enhances anti-tumor immunity in glioblastoma.
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中文摘要
胶质母细胞瘤（GBM）是最常见且侵袭性最强的原发性脑肿瘤；对于大多数接受标准治疗的患者而言，仍存在重大的未满足医疗需求。近期，工程化溶瘤单纯疱疹病毒（oHSV）临床试验结果显示溶瘤疗法在GBM中的潜力，但疗效仍有限。本文报告一种新型溶瘤单纯疱疹病毒HSV-SUR15，有望为GBM提供新的治疗策略。HSV-SUR15利用肿瘤特异性survivin启动子恢复病毒神经毒力基因ICP34.5和核糖核苷酸还原酶基因ICP6，从而增强病毒在肿瘤细胞中的复制和细胞毒作用。同时，HSV-SUR15可通过分泌白细胞介素15（IL-15）激活T细胞和自然杀伤（NK）细胞。研究发现，这一联合策略协同增强了oHSV建立持久肿瘤特异性免疫反应的能力，并在胶质母细胞瘤小鼠模型中有效抑制肿瘤生长。本研究克服了oHSV或IL-15单药治疗固有的局限，为GBM临床治疗提供了有价值的依据。
展开英文摘要原文
Glioblastoma (GBM) is the most prevalent and aggressive primary brain tumor, and remains a major unmet medical need for most patients on the standard treatment regimen. Recently, clinical trial results using engineered oncolytic herpes simplex virus (oHSV) have illuminated the potential of oncolytic therapy in GBM but have also shown limited success.
Here, we report a novel oncolytic herpes simplex virus HSV-SUR15, that may offer a promising treatment strategy for GBM. HSV-SUR15 utilizes a tumor-specific survivin promoter to restore the viral neurovirulence ICP34. 5 gene and ribonucleotide reductase ICP6 gene, enhancing viral replication and cytotoxicity specifically in tumor cells. Simultaneously, HSV-SUR15 can also activate T cells and natural killer (NK) cells by secreting interleukin-15 (IL-15).
We found that this combination strategy synergistically enhanced the ability of oHSV to establish durable tumor-specific immune responses, and effectively suppressed tumor growth in mouse models of glioblastoma.
Our study effectively overcomes the inherent limitations of oHSV and IL-15 monotherapy, providing valuable insights for the clinical treatment of GBM.
论文信息
- 作者
- Xu L、Yang N、Lu H、Zhang Z、Chen Y、Liu N、Zhang X、Jiang L
- 第一作者单位
- State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.China
- 通讯作者单位
- State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China; Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China. Electronic address: aipingtong@scu.edu.cn.China
- 期刊
- International immunopharmacology2026 Jan 1
- 原文标识
- PubMed 41197268 · DOI 10.1016/j.intimp.2025.115780