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

Author

Listed:
  • Michael F. Cuccarese

    (Center for Systems Biology, Massachusetts General Hospital)

  • J. Matthew Dubach

    (Center for Systems Biology, Massachusetts General Hospital
    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
    Massachusetts General Hospital)

  • Mikael J. Pittet

    (Center for Systems Biology, Massachusetts General Hospital
    Massachusetts General Hospital)

  • Ralph Weissleder

    (Center for Systems Biology, Massachusetts General Hospital
    Massachusetts General Hospital
    Harvard Medical School)

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.

Suggested Citation

  • Michael F. Cuccarese & J. Matthew Dubach & Christina Pfirschke & Camilla Engblom & Christopher Garris & Miles A. Miller & Mikael J. Pittet & Ralph Weissleder, 2017. "Heterogeneity of macrophage infiltration and therapeutic response in lung carcinoma revealed by 3D organ imaging," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14293
    DOI: 10.1038/ncomms14293
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    Cited by:

    1. Ruixue Qin & Shi Li & Yuwei Qiu & Yushuo Feng & Yaqing Liu & Dandan Ding & Lihua Xu & Xiaoqian Ma & Wenjing Sun & Hongmin Chen, 2022. "Carbonized paramagnetic complexes of Mn (II) as contrast agents for precise magnetic resonance imaging of sub-millimeter-sized orthotopic tumors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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