Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging

被引：149

作者：

Cuccarese, Michael F. ^{[1
]}

Dubach, J. Matthew ^{[1
,2
]}

Pfirschke, Christina ^{[1
]}

Engblom, Camilla ^{[1
]}

Garris, Christopher ^{[1
]}

Miller, Miles A. ^{[1
,2
]}

Pittet, Mikael J. ^{[1
,2
]}

Weissleder, Ralph ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Radiol, 185 Cambridge St,CPZN 5206, Boston, MA 02114 USA

[3] Harvard Med Sch, Dept Syst Biol, 200 Longwood Ave, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

关键词：

TUMOR-ASSOCIATED MACROPHAGES; MYELOID CELLS; IMMUNE CELLS; BLOCKADE; NANOPARTICLES; POLARIZATION; INHIBITION; DYNAMICS; KINASE; PROBES;

D O I：

10.1038/ncomms14293

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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