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

Michael F. Cuccarese, J. Matthew Dubach, Christina Pfirschke, Camilla Engblom, Christopher Garris, Miles A. Miller, Mikael J. Pittet () and Ralph Weissleder ()
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Michael F. Cuccarese: Center for Systems Biology, Massachusetts General Hospital
J. Matthew Dubach: Center for Systems Biology, Massachusetts General Hospital
Christina Pfirschke: Center for Systems Biology, Massachusetts General Hospital
Camilla Engblom: Center for Systems Biology, Massachusetts General Hospital
Christopher Garris: Center for Systems Biology, Massachusetts General Hospital
Miles A. Miller: Center for Systems Biology, Massachusetts General Hospital
Mikael J. Pittet: Center for Systems Biology, Massachusetts General Hospital
Ralph Weissleder: Center for Systems Biology, Massachusetts General Hospital

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14293

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DOI: 10.1038/ncomms14293

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