Imaging endogenous macrophage iron deposits reveals a metabolic biomarker of polarized tumor macrophage infiltration and response to CSF1R breast cancer immunotherapy Journal Article

   

Authors:	Leftin, A.; Ben-Chetrit, N.; Joyce, J. A.; Koutcher, J. A.
Article Title:	Imaging endogenous macrophage iron deposits reveals a metabolic biomarker of polarized tumor macrophage infiltration and response to CSF1R breast cancer immunotherapy
Abstract:	Iron deposits are a phenotypic trait of tumor-associated macrophages (TAMs). Histological iron imaging and contrast-agent free magnetic resonance imaging (MRI) can detect these deposits, but their presence in human cancer, and correlation with immunotherapeutic response is largely untested. Here, primarily using these iron imaging approaches, we evaluated the spatial distribution of polarized macrophage populations containing high endogenous levels of iron in preclinical murine models and human breast cancer, and used them as metabolic biomarkers to correlate TAM infiltration with response to immunotherapy in preclinical trials. Macrophage-targeted inhibition of the colony stimulating factor 1 receptor (CSF1R) by immunotherapy was confirmed to inhibit macrophage accumulation and slow mammary tumor growth in mouse models while also reducing hemosiderin iron-laden TAM accumulation as measured by both iron histology and in vivo iron MRI (FeMRI). Spatial profiling of TAM iron deposit infiltration defined regions of maximal accumulation and response to the CSF1R inhibitor, and revealed differences between microenvironments of human cancer according to levels of polarized macrophage iron accumulation in stromal margins. We therefore demonstrate that iron deposition serves as an endogenous metabolic imaging biomarker of TAM infiltration in breast cancer that has high translational potential for evaluation of immunotherapeutic response. © 2019, The Author(s).
Journal Title:	Scientific Reports
Volume:	9
ISSN:	2045-2322
Publisher:	Nature Publishing Group
Date Published:	2019-01-29
Start Page:	857
Language:	English
DOI:	10.1038/s41598-018-37408-7
PUBMED:	30696910
PROVIDER:	scopus
PMCID:	PMC6351660
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060803805&doi=10.1038%2fs41598-018-37408-7&partnerID=40&md5=7df2f6a4d18f9ec8236a852f732359a8
Notes:	Article -- Export Date: 1 March 2019 -- Source: Scopus

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