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
靶向 PVR-TIGIT/CD96/CD226 信号通路的胶质瘤免疫治疗策略
英文原题：Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.
查看英文原题
Immunotherapeutic strategies targeting the PVR-TIGIT/CD96/CD226 signaling pathway in glioma treatment.
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研究概要
PVR-TIGIT/CD96/CD226 轴是胶质瘤中一个关键的免疫检查点。靶向破坏这一通路为克服耐药和改善临床结局提供了一种有前景的策略。
研究思路结论见上方概要
背景
总结脊髓灰质炎病毒受体（PVR）与其受体（抑制性 TIGIT/CD96 和激活性 CD226）的分子相互作用，阐明这些相互作用如何驱动胶质瘤免疫逃逸，并评估新兴的 PVR 导向治疗策略。
方法
胶质瘤中PVR通路生物学与药物开发的临床前及临床数据（至2025年）的关键性综合
结果
PVR 与 TIGIT/CD96 结合可抑制 T 细胞和 NK 细胞的细胞毒性，使细胞因子谱向调节性表型偏移，并削弱肿瘤细胞死亡；同时 CD226 的参与被竞争性拮抗，从而放大免疫逃逸。PVR 表达升高与效应细胞浸润减少、Treg 和耗竭 T 细胞特征增加以及患者预后较差相关。通过单克隆抗体（如抗 TIGIT/CD96）、双特异性衔接分子和 CAR 修饰的 T/NK 细胞阻断 PVR，可在临床前胶质瘤模型中恢复抗肿瘤免疫，早期临床试验正在进行中。
展开英文摘要原文
BACKGROUND
To summarise the molecular interactions of Poliovirus Receptor (PVR) with its receptors (inhibitory TIGIT/CD96 and activating CD226), to delineate how these interactions drive glioma immune escape, and to evaluate emerging PVR-directed therapeutic strategies.
METHODS
Critical synthesis of pre-clinical and clinical data (to 2025) on PVR pathway biology and drug development in glioma.
RESULTS
PVR ligation of TIGIT/CD96 suppresses T- and NK-cell cytotoxicity, skews cytokine profiles toward regulatory phenotypes, and blunts tumour cell death; concurrent CD226 engagement is competitively antagonised, amplifying immune escape. Elevated PVR expression correlates with reduced effector infiltration, increased Treg and exhausted T-cell signatures, and inferior patient prognosis. PVR blockade via monoclonal antibodies (e.g. anti-TIGIT/CD96), bispecific engagers, and CAR-modified T/NK cells restores anti-tumour immunity in pre-clinical glioma models, with early-phase trials underway.
CONCLUSIONS
The PVR-TIGIT/CD96/CD226 axis is a critical immune checkpoint in glioma. Targeted disruption of this pathway offers a promising strategy to overcome resistance and improve clinical outcomes.
论文信息
- 作者
- Qian D、Guo J、Duan Y、Zhou Y、Wu C、Chen Q、Cai J
- 第一作者单位
- Central Laboratory, Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu, China.China
- 通讯作者单位
- Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.China
- 文献类型
- 综述 · 非美国政府资助研究
- 期刊
- Annals of medicine2025 Dec
- 原文标识
- PubMed 41254994 · DOI 10.1080/07853890.2025.2588717
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