Iron induces anti-tumor activity in tumor-associated macrophages
Open accessAbstract
Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment. Here we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the tumor microenvironment. The occurrence of iron-loaded TAMs (iTAMs) correlated with reduced tumor size in patients with non-small cell lung cancer. Ex vivo experiments established that TAMs exposed to hemolytic red blood cells were converted into pro-inflammatory macrophages capable of directly killing tumor cells. This anti-tumor effect could also be elicited via iron oxide nanoparticles. When tested in vivo, tumors injected with such iron oxide nanoparticles led to significantly smaller tumor sizes compared to controls. These results identify hemolytic red blood cells and iron as novel players in the tumor microenvironment that repolarize TAMs to exert direct anti-tumor effector function. Thus, the delivery of iron to TAMs emerges as a simple adjuvant therapeutic strategy to promote anti-cancer immune responses.
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In lung cancer, iron-laden TAMs enhance production of ROS and pro-inflammatory cytokines (TNFα and IL-6) and directly kill tumor cells.
“In lung cancer for example, iron-laden TAMs have been demonstrated to enhance production of ROS and pro-inflammatory cytokines (TNFα and IL-6) and to directly kill tumor cells (da Silva et al., 2017), prompting the exciting possibility of delivering iron to TAMs as a simple adjuvant therapeutic strategy.”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as da Silva et al., 2017
Excess amounts of heme or iron in hemorrhagic tumor areas are detrimental to the macrophage iron phenotype by shifting the anti-inflammatory, pro-tumor macrophage phenotype to a pro-inflammatory and thus anti-tumoral one.
“However, recent findings suggest that excess amounts of heme or iron in hemorrhagic tumor areas are detrimental to the macrophage iron phenotype by shifting the anti-inflammatory, pro-tumor macrophage phenotype to a pro-inflammatory and thus anti-tumoral one [77].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [77]
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- Authors
- Costa da Silva, M., Breckwoldt, M. O., Vinchi, F., Correia, M. P., Stojanovic, A., Thielmann, C. M., Meister, M., Muley, T., Warth, A., Platten, M., Hentze, M. W., Cerwenka, A., & Muckenthaler, M. U.
- Affiliations
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- Corresponding author
- Muckenthaler, Martina U.
- ORCID
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2017-11-08
- Volume
- 8
- Pages
- 1479-1479
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC5682327
- OpenAlex
- W2767749438
- Cited by
- 164
- References
- 73
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 20 · 2023: 26 · 2022: 16 · 2021: 36 · 2020: 17 · 2019: 16 · 2018: 11
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação para a Ciência e a Tecnologia (SFRH/BD/51290/2010)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tumor-associated macrophages, iron, non-small cell lung cancer, tumor microenvironment, iron oxide nanoparticles, macrophage repolarization, anticancer activity, tumor immunosuppression, adjuvant therapy
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