AUTHOR=Costa da Silva Milene , Breckwoldt Michael O. , Vinchi Francesca , Correia Margareta P. , Stojanovic Ana , Thielmann Carl Maximilian , Meister Michael , Muley Thomas , Warth Arne , Platten Michael , Hentze Matthias W. , Cerwenka Adelheid , Muckenthaler Martina U. 

TITLE=Iron Induces Anti-tumor Activity in Tumor-Associated Macrophages

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01479

DOI=10.3389/fimmu.2017.01479

ISSN=1664-3224

ABSTRACT=<p>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. <italic>Ex vivo</italic> 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 <italic>via</italic> iron oxide nanoparticles. When tested <italic>in vivo</italic>, 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.</p>