Iron deposition is associated with differential macrophage infiltration and therapeutic response to iron chelation in prostate cancer
Open accessAbstract
Immune cells such as macrophages are drivers and biomarkers of most cancers. Scoring macrophage infiltration in tumor tissue provides a prognostic assessment that is correlated with disease outcome and therapeutic response, but generally requires invasive biopsy. Routine detection of hemosiderin iron aggregates in macrophages in other settings histologically and in vivo by MRI suggests that similar assessments in cancer can bridge a gap in our ability to assess tumor macrophage infiltration. Quantitative histological and in vivo MRI assessments of non-heme cellular iron revealed that preclinical prostate tumor models could be differentiated according to hemosiderin iron accumulation-both in tumors and systemically. Monitoring cellular iron levels during "off-label" administration of the FDA-approved iron chelator deferiprone evidenced significant reductions in tumor size without extensive perturbation to these iron deposits. Spatial profiling of the iron-laden infiltrates further demonstrated that higher numbers of infiltrating macrophage iron deposits was associated with lower anti-tumor chelation therapy response. Imaging macrophages according to their innate iron status provides a new phenotypic window into the immune tumor landscape and reveals a prognostic biomarker associated with macrophage infiltration and therapeutic outcome.
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The iron-donating macrophage phenotype was directly linked to enhanced tumor cell proliferation and growth, both in vitro and in vivo.
“This iron-donating macrophage phenotype was directly linked to enhanced tumor cell proliferation and growth, both in vitro and in vivo [64,66,67,70,71,72].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [71]
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References 57 · Cited by 33
Research works printed but not linked: 2
- [52]Porter, J., Viprakasit, V. & Kattamis, A. Iron overload and chelation. in Guidelines for the management of transfusion dependent thalassaemia (ed. Cappelinni, M. D, C. A., Porter, J, et. al) (Nicosia (CY): Thalassaemia International Federation, 2014). 25610943
- [54]Sage, D., Prodanov, D., Tinevez, J.-Y. & Schindelin, J. MIJ: making interoperability between ImageJ and Matlab possible. in ImageJ User and Developer Conference (Luxembourg, 2012).
- Authors
- Leftin, A., Zhao, H., Turkekul, M., de Stanchina, E., Manova, K., & Koutcher, J. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Koutcher, Jason A.
- Venue
- Scientific Reports
- Published
- 2017-09-14
- Volume
- 7
- Issue
- 1
- Pages
- 11632-11632
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5599545
- OpenAlex
- W2755414624
- Cited by
- 33
- References
- 57
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (P30CA008748, CA115675, CA008748, 1F32CA206277, PC120233)
- Memorial Sloan-Kettering Cancer Center (CA008748, P30 CA008748, NCI P30 CA008748)
- National Institutes of Health (NCI P30, 5f32ca206277-02, CA008748, NCI P30CA008748, 1F32CA206277, PO1-CA115675, CA115675)
- National Cancer Institute (CA115675, CA008748, F32 CA206277, NCI P30 CA008748, PO1 CA115675, P01CA115675, 1F32CA206277, P30CA008748)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Keywords
- prostate cancer, tumor-associated macrophages, iron chelation, deferiprone, macrophage infiltration, prognostic factors, treatment response, preclinical cancer models, tumor immune microenvironment
- MeSH terms
- CD68 Molecule, Animals, Disease Models, Animal, Humans, Iron, Iron Chelating Agents, Macrophages, Magnetic Resonance Imaging, Male, Prostatic Neoplasms, Antigens, Differentiation, Myelomonocytic, Biomarkers, Antigens, CD, Xenograft Model Antitumor Assays, Mice, Tumor Microenvironment
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