Pneumologie 2015; 69 - A75
DOI: 10.1055/s-0035-1556667

Iron levels define two populations of Tumor Associated Macrophages

M Costa da Silva 1, 2, 3, M Correia 2, F Vinchi 1, A Cerwenka 2, MU Muckenthaler 1
  • 1Molecular medicine Partnership Unit – University of Heidelberg, Department of Pediatric Oncology, Hematology and Immunology, Heidelberg, Germany
  • 2German Cancer Research Center (DKFZ), Heidelberg, Germany
  • 3Graduate Program in Areas of Basic and Applied Biology, Abel Salazar Biomedical Sciences Institute, University of Porto, Portugal

Tumor-associated macrophages (TAMs) play an important role in the tumor microenvironment. TAMs acquire a M2-like macrophage phenotype and contribute to tissue remodeling, tumor growth and angiogenesis, hallmarks for cancer invasion. Likely, they also recycle iron from erythrocytes released as a consequence of angiogenesis in the tumor or retain iron upon tumor-related inflammation. The functional consequences of iron accumulation in TAMS are not well established. Here, we investigated whether iron levels affect TAM polarization and function and/or influence tumor growth.

Macrophage subpopulations were studied in a mouse model of Lewis Lung Carcinoma (LLC) and macrophage infiltration and iron-related parameters were analyzed by FACS, iron measurements, histology, immunohistochemistry, RT-qPCR and co-culture of macrophages and cancer cells. In addition, iron distribution was studied in human histological slides from lung cancer patients.

Both, in lung cancer patients and in a mouse model for LLC we detected two populations of TAMs that differed in their iron content. Interestingly, the iron levels in the TAMs correlates with the differentiation state of the macrophages: iron-loaded macrophages are of the inflammatory (M1-like) phenotype, whereas iron-spared macrophages polarize towards the M2-like phenotype. Co-culturing of LLC cells and macrophages induce the polarization of the macrophages towards an M2-like phenotype. Interestingly, this can be shifted to a M1-like inflammatory phenotype by applying different sources of iron.

We show that iron can influence macrophage differentiation in the tumor microenvironment. We described two different populations of iron-related TAMs that might have relevant impact for cancer cell proliferation and the metastatic potential of the tumor.

*Presenting author