Early Therapeutic Vaccination Prediction of Hepatocellular Carcinoma via Imaging OX40-Mediated Tumor Infiltrating Lymphocytes
Early Therapeutic Vaccination Prediction of Hepatocellular Carcinoma via Imaging OX40-Mediated Tumor Infiltrating Lymphocytes
复制标题
通过 OX40 介导的肿瘤浸润淋巴细胞成像预测肝细胞癌的早期治疗性疫苗接种
DOI：
10.1021/acs.molpharmaceut.9b00590
复制
发表时间：
2019-10-01
影响因子：
4.9
通讯作者：
Shan, Hong
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyun;Li, Dan;Shan, Hong
肝细胞癌（HCC）患者的总体预后很差，但免疫策略可能是治疗HCC的一种新的有效工具。然而，肝癌免疫应答的早期预测仍然是一个很大的挑战。我们开发了一种新的近红外荧光（NIRF）探针（IRDye 800-AbOX 40）用于OX 40靶向成像。建立荷H22双瘤小鼠模型，采用CpG ODN瘤内免疫治疗。接种后16小时，通过尾静脉向小鼠注射探针，并进行NIRF成像。该探针在HCC肿瘤中的摄取早在接种后40小时就大大增加，并在54和112小时之间达到平台期，而未处理的肿瘤显示出较低的摄取，这通过离体成像和流式细胞术进一步证实。免疫荧光染色鉴定了CD 3和OX 40在肿瘤微环境中的共定位。免疫组化结果显示，肿瘤浸润淋巴细胞（TIL）上OX 40的表达水平与H22肿瘤的荧光信号相关。IRDye 800-AbOX 40可作为特异性NIRF探针，无创性检测TIL上OX 40的表达，有助于预测HCC免疫治疗的早期反应。
The overall prognosis for hepatocellular carcinoma (HCC) patients is poor but immunotherapeutic strategies may represent a novel and effective tool for HCC. However, the prediction of the early response for the immunotherapeutic effect of HCC remains a big challenge. We developed a novel near-infrared fluorescence (NIRF) probe (IRDye800-AbOX40) for OX40-targeted imaging. The H22 dual-tumor-bearing mice models were established and treated with CpG ODN intratumoral vaccination. Sixteen hours after vaccination, the mice were injected with the probe via the tail vein and conducted with NIRF imaging. The uptake of this probe in HCC tumors was greatly increased as early as 40 h post vaccination and reached a plateau between 54 and 112 h, while the untreated tumors showed a lower uptake, which was further confirmed by ex vivo imaging and flow cytometry. Immunofluorescence staining identified the colocalization of CD3 and OX40 in the tumor microenvironment. Moreover, immunohistochemistry analysis showed that OX40 expression level on tumor infiltrating lymphocytes (TILs) was associated with the fluorescence signal of the H22 tumors. IRDye800-AbOX40 could be used as a specific NIRF probe for noninvasive imaging of OX40 expression on TILs, which may aid in predicting the early response to immunotherapy of HCC.