Macrophage Responses to Hypoxia
Open accessAbstract
The presence of multiple areas of hypoxia (low oxygen tension) is a hallmark feature of human and experimental tumors. Monocytes are continually recruited into tumors, differentiate into tumor-associated macrophages (TAMs), and then accumulate in these hypoxic areas. A number of recent studies have shown that macrophages respond to the levels of hypoxia found in tumors by up-regulating such transcription factors as hypoxia-inducible factors 1 and 2, which in turn activate a broad array of mitogenic, pro-invasive, pro-angiogenic, and pro-metastatic genes. This could explain why high numbers of TAMs correlate with poor prognosis in various forms of cancer. In this review, we assess the evidence for hypoxia activating a distinct, pro-tumor phenotype in macrophages and the possible effect of this on the growth, invasion, angiogenesis, and immune evasion of tumors. We also discuss current attempts to selectively target TAMs for destruction or to use them to deliver gene therapy specifically to hypoxic tumor sites.
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Macrophages accumulate in hypoxic environments to release prohealing and pro-angiogenic factors such as VEGF, PDGF and enzymes such as COX2.
“Macrophages accumulate in hypoxic environments to release prohealing and pro-angiogenic factors such as vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) [63] and enzymes such as Cyclooxygenase 2 (COX2) [64].”
From Biomaterial based modulation of macrophage polarization: a review and suggested design principles (2015) · cites this paper as [64]
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- Authors
- Lewis, C., & Murdoch, C.
- Affiliations
- University of Sheffield (GB)
- Corresponding author
- Lewis, Claire
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 167
- Issue
- 3
- Pages
- 627-635
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC1698733
- OpenAlex
- W1515730558
- Cited by
- 413
- References
- 155
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 12 · 2023: 16 · 2022: 15 · 2021: 16 · 2020: 19 · 2019: 21 · 2018: 13 · 2017: 25 · 2016: 19 · 2015: 17 · 2014: 26 · 2013: 20 · 2012: 27
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- School of Medicine, University of North Carolina at Chapel Hill
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- tumor-associated macrophages, hypoxia, HIF-1, HIF-2, tumor microenvironment, tumor invasion, tumor angiogenesis, metastasis, immune evasion, macrophage polarization, TAM-targeted therapy
- MeSH terms
- Animals, Hypoxia, Humans, Macrophages, Neoplasms, Disease Progression
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