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首页> 美国卫生研究院文献>Theranostics >Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment
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Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment

机译：肿瘤免疫相互作用的可视化-S100A8 / A9的目标特异性成像揭示了转移前的利基建立。

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Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming.Methods A syngeneic model system for invasive breast cancer with (4T1.2) or without (67NR) the tendency to form lung metastasis was established in BALB/c mice. A SPECT-probe has been generated and tested for visualization of S100A9 release. Tumor-associated changes in numbers and fuction of immune cells in pre-metastatic tissue were evaluated by flow cytometry and confocal microscopy.Results S100A8/A9 imaging reflected MDSC abundance and the establishment of an immunosuppressive environment in pre-metastatic lung tissue (activity 4T1.2 vs. healthy control: 0.95 vs. 0.45 %ID; p<0.001). The S100A8/A9 imaging signal in the pre-metastatic lung correlated with the subsequent metastatic tumor burden in the same organ (r2=0.788; p<0.0001). CCL2 blockade and the consecutive inhibition of premetastatic niche establishment was clearly depicted by S100A9-SPECT (lung activity untreated vs. treated: 2 vs, 1.4 %ID).Conclusion We report S100A8/A9 as a potent imaging biomarker for tumor-mediated immune remodeling with potential applications in basic research and clinical oncology.
机译：背景技术在全身性癌症扩散之前，要在转移的目标组织-转移前的利基中建立允许的微环境。作为建立转移前利基的关键因素，髓样来源的抑制细胞（MDSC）释放S100A8 / A9，这是一种有助于转移，血管生成和免疫抑制的外泌体蛋白。我们报道了基于抗体的单光子发射计算机断层扫描（SPECT）在体内检测S100A8 / A9作为转移前组织启动的成像标志物的方法。方法（4T1.2 ）或没有（67NR）的情况下，在BALB / c小鼠中已确定形成肺转移的趋势。已经生成了SPECT探针，并对其进行了可视化的S100A9版本测试。通过流式细胞术和共聚焦显微镜评估了转移前肿瘤组织中肿瘤相关免疫细胞数量和功能的变化。结果S100A8 / A9成像反映了转移前肺组织中MDSC的丰度和免疫抑制环境的建立（活性4T1。 2对健康对照组：0.95对0.45％ID； p <0.001）。转移前肺中的S100A8 / A9成像信号与同一器官中随后的转移性肿瘤负荷相关（r 2 = 0.788； p <0.0001）。 S100A9-SPECT清楚地描述了CCL2的阻滞和对转移前生态位建立的连续抑制（未治疗与治疗的肺活量：2 vs，1.4％ID）。结论我们报道S100A8 / A9是有效的影像学生物标记物，可用于肿瘤介导的免疫重塑在基础研究和临床肿瘤学中具有潜在的应用。

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