Hypoxia-inducible factors as key regulators of tumor inflammation
Open accessAbstract
Low levels of oxygen or hypoxia is often an obstacle in health, particularly in pathological disorders like cancer. The main family of transcription factors responsible for cell survival and adaptation under strenuous conditions of hypoxia are the “hypoxia‐inducible factors” (HIFs). Together with prolyl hydroxylase domain enzymes (PHDs), HIFs regulates tumor angiogenesis, proliferation, invasion, metastasis, in addition to resistance to radiation and chemotherapy. Additionally, the entire HIF transcription cascade is involved in the “seventh” hallmark of cancer; inflammation. Studies have shown that hypoxia can influence tumor associated immune cells toward assisting in tumor proliferation, differentiation, vessel growth, distant metastasis and suppression of the immune response via cytokine expression alterations. These changes are not necessarily analogous to HIF's role in non‐cancer immune responses, where hypoxia often encourages a strong inflammatory response.
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TAMs accumulate in hypoxic areas and the tumor microenvironment through HIF-1α activation, which promotes their adaptation to hypoxia.
“For example, TAMs accumulate in hypoxic areas and the TME through HIF-1α activation, promoting TAM adaptation to hypoxia [2, 72].”
From The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation (2025) · cites this paper as [72]
The Macrophages section (page unavailable) says TAMs accumulate in hypoxic tumor regions, where they upregulate HIF-1α and HIF-2α. It does not say HIF-1α activation causes that accumulation or establishes that it promotes TAM adaptation to hypoxia; the Mini Review section instead links TAM migration in the models discussed to HIF-2α. (LLM, conf=0.88)
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Hypoxia‐inducible factors in regulation of immune responses in tumour microenvironment
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The HIF Axes in Cancer - Angiogenesis, Metabolism and Immune-Modulation
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- Authors
- Mamlouk, S., & Wielockx, B.
- Affiliations
- Technische Universität Dresden (DE)
- Center for Regenerative Therapies Dresden (DE)
- Corresponding author
- Wielockx, Ben
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2012-11-02
- Volume
- 132
- Issue
- 12
- Pages
- 2721-2729
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W1991886838
- Cited by
- 61
- References
- 145
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 9 · 2014: 9 · 2013: 2
- FWCI
- 0.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Technische Universität Dresden
- Topics
- 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
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- hypoxia-inducible factor, tumor hypoxia, tumor inflammation, tumor angiogenesis, metastasis, chemoresistance, radioresistance (biology), tumor-infiltrating immune cells, cytokine expression, cancer hallmarks
- MeSH terms
- Animals, Humans, Inflammation, Neoplasm Metastasis, Neoplasms, Neovascularization, Pathologic, Signal Transduction, Cell Hypoxia, Zinc Fingers, Hypoxia-Inducible Factor 1
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