Cited by 413Immune cells in cancerCancer, Hypoxia, and MetabolismAngiogenesis and VEGF in Cancer

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Macrophage Responses to Hypoxia

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Lewis, Claire, Murdoch, Craig·2005·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)62038-xPMC PMC1698733

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Abstract

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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Authors: Lewis, C., & Murdoch, C.
Affiliations: University of Sheffield (GB)
Corresponding author: Lewis, Claire
ORCID: Lewis, Claire
Murdoch, Craig
Venue: The American Journal of Pathology
Publisher: Elsevier BV
Published: 2005-09
Volume: 167
Issue: 3
Pages: 627-635
ISSN: 0002-9440 (ISSN-L)
DOI: 10.1016/s0002-9440(10)62038-x
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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