Immunotherapies have emerged as an effective treatment option for immune-related diseases, such as cancer and inflammatory diseases. However, variations in patient responsiveness limit the broad applicability and success of these immunotherapies. Noninvasive whole-body imaging of the immune status of individual patients during immunotherapy could enable the prediction and monitoring of the patient’s response, resulting in more personalized treatments. In this study, we developed a nanobody-based immunotracer targeting CD163, a receptor specifically expressed on macrophages. This anti-CD163 immunotracer bound to human and mouse CD163 with high affinity and specificity without competing for ligand binding. Furthermore, the tracer showed no unwanted immune cell activation and was nonimmunogenic. Upon radiolabeling of the anti-CD163 immunotracer, specific imaging of CD163 + macrophages using micro-single-photon emission computerized tomography/computed tomography or micro-positron emission tomography/CT was performed. The anti-CD163 immunotracer was able to stratify immunotherapy responders from nonresponders (NR) by visualizing differences in the intratumoral CD163 + TAM distribution in Lewis lung carcinoma-ovalbumin tumor-bearing mice receiving an anti-programmed cell death protein-1 (PD-1)/CSF1R combination treatment. Immunotherapy-responding mice showed a more homogeneous distribution of the PET signal in the middle of the tumor, while CD163 + TAMs were located at the tumor periphery in NR. As such, visualization of CD163 + TAM distribution in the tumor microenvironment could allow a prediction or follow-up of therapy response. Altogether, this study describes an immunotracer, specific for CD163 + macrophages, that allows same-day imaging and follow-up of these immune cells in the tumor microenvironment, providing a good basis for the prediction and follow-up of immunotherapy responses in cancer patients.

中文翻译：

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使用 CD163 特异性纳米抗体免疫示踪剂对免疫治疗过程中肿瘤相关的巨噬细胞动力学进行成像


免疫疗法已成为免疫相关疾病（如癌症和炎症性疾病）的有效治疗选择。然而，患者反应的差异限制了这些免疫疗法的广泛适用性和成功率。在免疫治疗期间对个体患者的免疫状态进行无创全身成像可以预测和监测患者的反应，从而实现更加个性化的治疗。在这项研究中，我们开发了一种靶向 CD163 的基于纳米抗体的免疫示踪剂，CD163 是一种在巨噬细胞上特异性表达的受体。这种抗 CD163 免疫示踪剂以高亲和力和特异性与人和小鼠 CD163 结合，而不会竞争配体结合。此外，示踪剂显示没有不需要的免疫细胞激活，并且具有非免疫原性。在抗 CD163 免疫示踪剂进行放射标记后，使用微单光子发射计算机断层扫描/计算机断层扫描或微正电子发射断层扫描/CT 对 CD163 + 巨噬细胞进行特异性成像。抗 CD163 免疫示踪剂能够通过可视化接受抗程序性细胞死亡蛋白-1 （PD-1）/CSF1R 联合治疗的 Lewis 肺癌-卵清蛋白荷瘤小鼠瘤内 CD163 + TAM 分布的差异，对免疫治疗反应者与无反应者 （NR） 进行分层。免疫治疗应答小鼠在肿瘤中间显示 PET 信号分布更均匀，而 CD163 + TAMs 在 NR 中位于肿瘤外围。因此，肿瘤微环境中 CD163 + TAM 分布的可视化可以预测或随访治疗反应。 总而言之，本研究描述了一种特异性于 CD163 + 巨噬细胞的免疫示踪剂，它可以在肿瘤微环境中对这些免疫细胞进行当天成像和随访，为癌症患者免疫治疗反应的预测和随访提供了良好的基础。