Abstract

Iron-loaded tumor-associated macrophages (iTAMs) show a pro-inflammatory phenotype, hallmarked by anti-tumorigenic activity and an ability to attenuate tumor growth. Here we explored the relevance of these findings in lung cancer patients by investigating the impact of the iTAM content in the tumor microenvironment (TME) on patient survival. We analyzed 102 human non-small cell lung cancer (NSCLC) paraffin-embedded archival tissue samples for iron levels and macrophage numbers. Interestingly, patients with lung adenocarcinoma accumulating iron in the TME show higher numbers of M1-like pro-inflammatory TAMs and a survival advantage compared to iron-negative patients. By contrast, in patients with lung squamous cell carcinoma iron in the TME does not affect survival, suggesting a unique influence of iron on different histological subtypes of non-small cell lung cancer (NSCLC). We conclude that in lung adenocarcinoma iron may serve as a prognostic marker for patient survival and as a potential therapeutic target for anti-cancer therapy.

Details

Title
Iron accumulation in tumor-associated macrophages marks an improved overall survival in patients with lung adenocarcinoma
Author
Thielmann, Carl Maximilian 1 ; Milene Costa da Silva 2 ; Muley, Thomas 3 ; Meister, Michael 3 ; Herpel, Esther 4 ; Muckenthaler, Martina U 1   VIAFID ORCID Logo 

1  Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), University of Heidelberg & EMBL, Heidelberg, Germany; Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany 
2  Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; Molecular Medicine Partnership Unit (MMPU), University of Heidelberg & EMBL, Heidelberg, Germany; Graduate Program in Areas of Basic and Applied Biology (GABBA), University of Porto, Porto, Portugal; German Cancer Research Center (DKFZ), University of Heidelberg, Heidelberg, Germany; Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany 
3  Translational Research Unit, Thoraxklinik, at University Hospital Heidelberg, Heidelberg, Germany; Translational Lung Research Center (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany 
4  Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, Germany 
Pages
1-9
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-47833-x
ProQuest document ID
2268792545
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.