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Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages
Milene Costa da Silva1,2,3,4,5, Michael O Breckwoldt6,7, Francesca Vinchi1,2
1Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.
Abstract:
Tumor-associated macrophages (TAMs) frequently help to sustain tumor growth and mediate immune suppression in the tumor microenvironment (TME). Here, we identified a subset of iron-loaded, pro-inflammatory TAMs localized in hemorrhagic areas of the TME. 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 (RBCs) 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 RBCs and iron as novel players in the TME 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.
Insights
Iron-loaded TAMs (tumor-associated macrophages) in hemorrhagic areas show anti-tumor effects. Delivering iron to TAMs repolarizes them to kill cancer cells, reducing tumor size in non-small cell lung cancer.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Tumor-associated macrophages (TAMs) often promote tumor growth and immune suppression within the tumor microenvironment (TME).
- Identifying novel mechanisms to repolarize TAMs towards an anti-tumor phenotype is crucial for cancer therapy.
Purpose of the Study:
- To investigate the role of iron-loaded TAMs (iTAMs) in the TME.
- To explore the potential of iron delivery as an adjuvant cancer therapy.
Main Methods:
- Identification and characterization of iTAMs in tumor samples.
- Ex vivo experiments exposing TAMs to hemolytic red blood cells (RBCs) and iron oxide nanoparticles.
- In vivo studies administering iron oxide nanoparticles to tumors.
Main Results:
- A subset of iron-loaded, pro-inflammatory TAMs was identified in hemorrhagic TME areas.
- Exposure to hemolytic RBCs or iron oxide nanoparticles converted TAMs into tumor-cell-killing macrophages.
- In vivo administration of iron oxide nanoparticles significantly reduced tumor size in non-small cell lung cancer models.
Conclusions:
- Hemolytic RBCs and iron can repolarize TAMs to exert direct anti-tumor functions.
- Iron delivery to TAMs represents a potential adjuvant therapeutic strategy to enhance anti-cancer immune responses.
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