Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging.
Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging.
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DOI：
10.1038/ncomms14293
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发表时间：
2017-02-08
影响因子：
16.6
通讯作者：
Weissleder R
中科院分区：
文献类型：
--
作者：
Cuccarese MF;Dubach JM;Pfirschke C;Engblom C;Garris C;Miller MA;Pittet MJ;Weissleder R
免疫系统参与肿瘤进展是癌症研究的前沿。对肿瘤免疫微环境的分析已经获得了丰富的肿瘤生物学信息，某些免疫亚型的变化，如肿瘤相关巨噬细胞()，可以作为强有力的预后指标。在这里，我们使用光学组织透明和靶向的可注射荧光纳米粒(NP)来检测三维成分、肿瘤到肿瘤的异质性、对集落刺激因子1受体(CSF1R)阻断的反应以及基于纳米粒的药物输送。该方法可以在整个肺的细胞水平上快速评估肿瘤体积和浸润的空间信息。该方法揭示了同一动物肿瘤间的密度是不均匀的，不同肺肿瘤模型的整体密度是不同的，纳米治疗药物的给药与的异质性相关，而对脑脊液-1R阻断的成功反应的特征是增强了在肿瘤内和肿瘤内的渗透。肿瘤相关巨噬细胞()可作为判断肿瘤预后的指标。在这里，作者建立了一个用于高通量3D显微镜的小鼠肺癌平台，允许可视化TAMS在整个肺的渗透、对CSF-1R阻断的反应和纳米药物输送。
Involvement of the immune system in tumour progression is at the forefront of cancer research. Analysis of the tumour immune microenvironment has yielded a wealth of information on tumour biology, and alterations in some immune subtypes, such as tumour-associated macrophages (TAM), can be strong prognostic indicators. Here, we use optical tissue clearing and a TAM-targeting injectable fluorescent nanoparticle (NP) to examine three-dimensional TAM composition, tumour-to-tumour heterogeneity, response to colony-stimulating factor 1 receptor (CSF-1R) blockade and nanoparticle-based drug delivery in murine pulmonary carcinoma. The method allows for rapid tumour volume assessment and spatial information on TAM infiltration at the cellular level in entire lungs. This method reveals that TAM density was heterogeneous across tumours in the same animal, overall TAM density is different among separate pulmonary tumour models, nanotherapeutic drug delivery correlated with TAM heterogeneity, and successful response to CSF-1R blockade is characterized by enhanced TAM penetration throughout and within tumours. Tumour-associated macrophages (TAM) can be used as prognostic indicators in cancer. Here, the authors establish a platform for high-throughput 3D microscopy in murine lung carcinoma that allows to visualize TAMs infiltration throughout the entire lung, response to CSF-1R blockade and nanoparticle drug delivery.