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dc.contributor.author
Weiler, Stefan
dc.contributor.author
Nairz, Manfred
dc.date.accessioned
2021-04-19T14:56:08Z
dc.date.available
2021-04-17T02:59:04Z
dc.date.available
2021-04-19T14:56:08Z
dc.date.issued
2021-03
dc.identifier.issn
2234-943X
dc.identifier.other
10.3389/fonc.2021.627223
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/479148
dc.identifier.doi
10.3929/ethz-b-000479148
dc.description.abstract
Cancer-induced anemia (CIA) is a common consequence of neoplasia and has a multifactorial pathophysiology. The immune response and tumor treatment, both intended to primarily target malignant cells, also affect erythropoiesis in the bone marrow. In parallel, immune activation inevitably induces the iron-regulatory hormone hepcidin to direct iron fluxes away from erythroid progenitors and into compartments of the mononuclear phagocyte system. Moreover, many inflammatory mediators inhibit the synthesis of erythropoietin, which is essential for stimulation and differentiation of erythroid progenitor cells to mature cells ready for release into the blood stream. These pathophysiological hallmarks of CIA imply that the bone marrow is not only deprived of iron as nutrient but also of erythropoietin as central growth factor for erythropoiesis. Tumor-associated macrophages (TAM) are present in the tumor microenvironment and display altered immune and iron phenotypes. On the one hand, their functions are altered by adjacent tumor cells so that they promote rather than inhibit the growth of malignant cells. As consequences, TAM may deliver iron to tumor cells and produce reduced amounts of cytotoxic mediators. Furthermore, their ability to stimulate adaptive anti-tumor immune responses is severely compromised. On the other hand, TAM are potential off-targets of therapeutic interventions against CIA. Red blood cell transfusions, intravenous iron preparations, erythropoiesis-stimulating agents and novel treatment options for CIA may interfere with TAM function and thus exhibit secondary effects on the underlying malignancy. In this Hypothesis and Theory, we summarize the pathophysiological hallmarks, clinical implications and treatment strategies for CIA. Focusing on TAM, we speculate on the potential intended and unintended effects that therapeutic options for CIA may have on the innate immune response and, consequently, on the course of the underlying malignancy.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Frontiers Research Foundation
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
cancer-induced anemia (CIA)
en_US
dc.subject
tumor-associated macrophage (TAM)
en_US
dc.subject
iron
en_US
dc.subject
hepcidin
en_US
dc.subject
ferroportin
en_US
dc.subject
BMP - Smad signaling pathway
en_US
dc.subject
IL-6 (interleukin 6)
en_US
dc.title
TAM-ing the CIA—Tumor-Associated Macrophages and Their Potential Role in Unintended Side Effects of Therapeutics for Cancer-Induced Anemia
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2021-03-25
ethz.journal.title
Frontiers in Oncology
ethz.journal.volume
11
en_US
ethz.pages.start
627223
en_US
ethz.size
17 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.scopus
ethz.publication.place
Lausanne
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2021-04-17T02:59:28Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-19T14:56:19Z
ethz.rosetta.lastUpdated
2022-03-29T06:39:03Z
ethz.rosetta.versionExported
true
ethz.COinS
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