Frontiers in Immunology (Nov 2017)
Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages
- Milene Costa da Silva,
- Milene Costa da Silva,
- Milene Costa da Silva,
- Milene Costa da Silva,
- Milene Costa da Silva,
- Michael O. Breckwoldt,
- Michael O. Breckwoldt,
- Francesca Vinchi,
- Francesca Vinchi,
- Margareta P. Correia,
- Ana Stojanovic,
- Carl Maximilian Thielmann,
- Carl Maximilian Thielmann,
- Michael Meister,
- Michael Meister,
- Thomas Muley,
- Thomas Muley,
- Arne Warth,
- Arne Warth,
- Michael Platten,
- Michael Platten,
- Matthias W. Hentze,
- Adelheid Cerwenka,
- Adelheid Cerwenka,
- Martina U. Muckenthaler,
- Martina U. Muckenthaler,
- Martina U. Muckenthaler
Affiliations
- Milene Costa da Silva
- Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
- Milene Costa da Silva
- Molecular Medicine Partnership Unit (MMPU), Heidelberg University, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Milene Costa da Silva
- Graduate Program in Areas of Basic and Applied Biology (GABBA), Abel Salazar Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal
- Milene Costa da Silva
- Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Milene Costa da Silva
- Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
- Michael O. Breckwoldt
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
- Michael O. Breckwoldt
- German Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Francesca Vinchi
- Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
- Francesca Vinchi
- Molecular Medicine Partnership Unit (MMPU), Heidelberg University, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Margareta P. Correia
- Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Ana Stojanovic
- Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Carl Maximilian Thielmann
- Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
- Carl Maximilian Thielmann
- Molecular Medicine Partnership Unit (MMPU), Heidelberg University, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Michael Meister
- Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
- Michael Meister
- Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
- Thomas Muley
- Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
- Thomas Muley
- Translational Research Unit, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany
- Arne Warth
- Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
- Arne Warth
- Institute of Pathology, University of Heidelberg, Heidelberg, Germany
- Michael Platten
- Department of Neuroradiology, University Hospital Heidelberg, Heidelberg, Germany
- Michael Platten
- German Cancer Consortium, Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Matthias W. Hentze
- Molecular Medicine Partnership Unit (MMPU), Heidelberg University, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Adelheid Cerwenka
- Innate Immunity Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Adelheid Cerwenka
- 0Division of Immunbiochemistry, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
- Martina U. Muckenthaler
- Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany
- Martina U. Muckenthaler
- Molecular Medicine Partnership Unit (MMPU), Heidelberg University, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany
- Martina U. Muckenthaler
- Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
- DOI
- https://doi.org/10.3389/fimmu.2017.01479
- Journal volume & issue
-
Vol. 8
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.
Keywords
- tumor-associated macrophages
- macrophage polarization
- hemolytic red blood cells
- heme
- iron
- non-small cell lung cancer
