CD81 通过阻断 CD274/PD-L1 的选择性自噬降解驱动放射抵抗性胶质母细胞瘤的免疫逃逸
CD81 drives immune evasion in radioresistant glioblastoma by blocking selective autophagic degradation of CD274/PD-L1.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD69 的免疫 PET 成像可显示小鼠胶质母细胞瘤中 T 细胞活化并预测免疫治疗后的生存
英文原题：Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival Following Immunotherapy in Murine Glioblastoma.
查看英文原题
Immuno-PET Imaging of CD69 Visualizes T-Cell Activation and Predicts Survival Following Immunotherapy in Murine Glioblastoma.
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中文摘要
胶质母细胞瘤（GBM）是成人中最常见且最具恶性的原发性脑肿瘤。免疫治疗可能对部分GBM患者的治疗具有前景；然而，需要无创神经影像技术来预测免疫治疗反应。大多数免疫治疗策略的有效性需要T细胞活化。因此，我们旨在评估T细胞活化的早期标志物CD69，作为GBM免疫治疗反应的影像生物标志物。在此，我们在体外活化后以及原位同基因小鼠胶质瘤模型接受免疫检查点抑制剂（ICI）治疗后，对人和小鼠T细胞进行了CD69免疫染色。使用接受ICI的复发性GBM患者的单细胞RNA测序（scRNA-seq）数据，评估了肿瘤浸润白细胞上的CD69表达。对荷GBM小鼠纵向进行了放射性标记CD69抗体PET/CT成像（CD69 immuno-PET），以量化CD69及其与免疫治疗后生存的关联。我们发现CD69表达在T细胞活化后以及响应免疫治疗的TIL（肿瘤浸润淋巴细胞）上上调。同样，scRNA-seq数据显示，与对照队列的TIL相比，ICI治疗的复发性GBM患者TIL上的CD69升高。CD69 immuno-PET研究显示，与对照组相比，ICI治疗小鼠肿瘤中的示踪剂摄取显著更高。重要的是，我们观察到免疫治疗动物中生存与CD69 immuno-PET信号之间存在正相关，并凭借CD69-immuno-PET测量建立了T细胞活化的轨迹。我们的研究支持CD69 immuno-PET作为GBM患者免疫治疗反应评估成像工具的潜在用途。意义：免疫治疗可能对部分GBM患者的治疗具有前景。需要评估治疗反应性，以便在应答者中继续有效治疗，并避免在无应答者中进行无效治疗及其潜在不良反应。我们证明，CD69的无创PET/CT成像可能有助于早期检测GBM患者的免疫治疗反应性。
展开英文摘要原文
UNLABELLED: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Immunotherapy may be promising for the treatment of some patients with GBM; however, there is a need for noninvasive neuroimaging techniques to predict immunotherapeutic responses. The effectiveness of most immunotherapeutic strategies requires T-cell activation.
Therefore, we aimed to evaluate an early marker of T-cell activation, CD69, for its use as an imaging biomarker of response to immunotherapy for GBM.
Herein, we performed CD69 immunostaining on human and mouse T cells following in vitro activation and post immune checkpoint inhibitors (ICI) in an orthotopic syngeneic mouse glioma model. CD69 expression on tumor-infiltrating leukocytes was assessed using single-cell RNA sequencing (scRNA-seq) data from patients with recurrent GBM receiving ICI. Radiolabeled CD69 Ab PET/CT imaging (CD69 immuno-PET) was performed on GBM-bearing mice longitudinally to quantify CD69 and its association with survival following immunotherapy.
We show CD69 expression is upregulated upon T-cell activation and on tumor-infiltrating lymphocytes (TIL) in response to immunotherapy. Similarly, scRNA-seq data demonstrated elevated CD69 on TILs from patients with ICI-treated recurrent GBM as compared with TILs from control cohorts. CD69 immuno-PET studies showed a significantly higher tracer uptake in the tumors of ICI-treated mice compared with controls.
Importantly, we observed a positive correlation between survival and CD69 immuno-PET signals in immunotherapy-treated animals and established a trajectory of T-cell activation by virtue of CD69-immuno-PET measurements.
Our study supports the potential use of CD69 immuno-PET as an immunotherapy response assessment imaging tool for patients with GBM. SIGNIFICANCE: Immunotherapy may hold promise for the treatment of some patients with GBM. There is a need to assess therapy responsiveness to allow the continuation of effective treatment in responders and to avoid ineffective treatment with potential adverse effects in the nonresponders.
We demonstrate that noninvasive PET/CT imaging of CD69 may allow early detection of immunotherapy responsiveness in patients with GBM.
论文信息
- 作者
- Nisnboym M、Vincze SR、Xiong Z、Sneiderman CT、Raphael RA、Li B、Jaswal AP、Sever RE
- 单位
- Department of Neurological Surgery, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.United States
- 文献类型
- 美国 NIH 资助研究 · 非美国政府资助研究
- 期刊
- Cancer research communications2023 Jul
- 原文标识
- PubMed 37426447 · DOI 10.1158/2767-9764.CRC-22-0434
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