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
胶质瘤微环境中 TIGIT 的免疫 PET 显像
英文原题：ImmunoPET imaging of TIGIT in the glioma microenvironment.
查看英文原题
ImmunoPET imaging of TIGIT in the glioma microenvironment.
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
胶质母细胞瘤（GBM）是最常见的原发性恶性脑肿瘤。目前，除手术和放化疗外，GBM 的有效治疗选择很少，即使采用这些干预措施，患者的中位生存期仍然很差。虽然免疫检查点抑制剂（ICIs）已证明对非中枢神经系统癌症具有治疗疗效，但针对 GBM 的 ICI 试验通常结果不佳。TIGIT 是一种免疫检查点受体，表达于活化的 T 细胞上，并在抑制 T 细胞和自然杀伤（NK）细胞功能中发挥作用。由于 TIGIT 表达既被报道为预后指标，也被报道为抗 TIGIT 治疗的生物标志物，我们构建了一种分子影像剂 [ 89 Zr]Zr-DFO-anti-TIGIT（89 Zr- TIGIT），以通过免疫PET成像在临床前 GBM 中可视化 TIGIT。89 Zr- TIGIT 的 PET 成像和生物分布分析显示其在 GBM 荷瘤小鼠的肿瘤微环境中有摄取。阻断抗体和无关抗体示踪剂研究证明了 89 Zr- TIGIT 的特异性，且在示踪剂注射后的晚期时间点具有显著性。
然而，相对于 IgG 示踪剂， 89 Zr- TIGIT 在肿瘤中的摄取幅度很小。这些发现突出了使用 89 Zr- TIGIT 在 GBM 微环境中可视化 TIGIT 的特征和局限性。
展开英文摘要原文
Glioblastoma (GBM) is the most common primary malignant brain tumor. Currently, there are few effective treatment options for GBM beyond surgery and chemo-radiation, and even with these interventions, median patient survival remains poor. While immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy against non-central nervous system cancers, ICI trials for GBM have typically had poor outcomes. TIGIT is an immune checkpoint receptor that is expressed on activated T-cells and has a role in the suppression of T-cell and Natural Killer (NK) cell function.
As TIGIT expression is reported as both prognostic and a biomarker for anti-TIGIT therapy, we constructed a molecular imaging agent, [ 89 Zr]Zr-DFO-anti-TIGIT ( 89 Zr- TIGIT), to visualize TIGIT in preclinical GBM by immunoPET imaging. PET imaging and biodistribution analysis of 89 Zr- TIGIT demonstrated uptake in the tumor microenvironment of GBM-bearing mice. Blocking antibody and irrelevant antibody tracer studies demonstrated specificity of 89 Zr- TIGIT with significance at a late time point post-tracer injection.
However, the magnitude of 89 Zr- TIGIT uptake in tumor, relative to the IgG tracer was minimal.
These findings highlight the features and limitations of using 89 Zr- TIGIT to visualize TIGIT in the GBM microenvironment.
论文信息
- 作者
- Vincze SR、Jaswal AP、Frederico SC、Nisnboym M、Li B、Xiong Z、Sever RE、Sneiderman CT
- 第一作者单位
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.United States
- 通讯作者单位
- Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. gary.kohanbash2@chp.edu.United States
- 期刊
- Scientific reports2024 Mar 4
- 原文标识
- PubMed 38438420 · DOI 10.1038/s41598-024-55296-y
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 →