The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer
Abstract
Both malignant and stromal components in tumors are influenced by the physiologic conditions of the microenvironment. Hypoxia is a prominent feature of solid tumors as a result of defective vascularization and intense metabolic activity. The gene-expression control mechanisms that adapt tissues to hypoxia are exploited by tumors to promote angiogenesis and vasculogenesis. The functions of infiltrating immune cells (macrophages and lymphocytes) and other stromal components are also influenced by a limited O(2) supply. Hypoxia-inducible factors (HIF) are the main molecular transcriptional mediators in the hypoxia response. The degradation and activity of HIF-1α and HIF-2α are tightly controlled by the fine-tuned action of oxygen-sensing prolyl and asparaginyl hydroxylase enzymes. Recent evidence indicates that hypoxia can modulate the differentiation and function of T lymphocytes and myeloid cells, skewing their cytokine-production profiles and modifying the expression of costimulatory receptors. This conceivably includes tumor-infiltrating lymphocytes. Hypoxia not only directly affects tumor-infiltrating leukocytes but also exerts effects on tumor cells and vascular cells that indirectly cause selective chemokine-mediated recruitment of suppressive and proangiogenic T-cell subsets. This review focuses on changes induced by hypoxia in immune cells infiltrating solid malignancies. Such changes may either promote or fight cancer, and thus are important for immunotherapy.
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In the citing paper
“Intratumoral hypoxia modulates the tumoral immune response in many ways, collectively pointing to an overall immunosuppressive effect (Palazon et al., 2012).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Palazon et al., 2012
In the citing paper
“Hypoxia can also suppress dendritic cell function and inhibit infiltrating cytotoxic T-lymphocyte activity in a HIF-1αdependent manner (Barsoum et al., 2014;Palazon et al., 2012).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Palazon et al., 2012
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Molecular mechanisms and clinical applications of angiogenesis
Carmeliet, P., & Jain, R. K. (2011) · Nature · doi:10.1038/nature10144 · Cited by 5,467
Macrophage Diversity Enhances Tumor Progression and Metastasis
Qian, B., & Pollard, J. W. (2010) · Cell · doi:10.1016/j.cell.2010.03.014 · Cited by 5,349
Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis
Shweiki, D., Itin, A., Soffer, D., & Keshet, E. (1992) · Nature · doi:10.1038/359843a0 · Cited by 4,617
Macrophage activation and polarization
Martinez, F. O. (2008) · Frontiers in Bioscience · doi:10.2741/2692 · Cited by 3,160
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Hypoxia-inducible factors and the response to hypoxic stress
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Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1
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Antiangiogenesis Strategies Revisited: From Starving Tumors to Alleviating Hypoxia
Jain, R. K. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.10.006 · Cited by 1,589
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687
Vascular Normalization as an Emerging Strategy to Enhance Cancer Immunotherapy
Huang, Y., Goel, S., Duda, D. G., Fukumura, D., & Jain, R. K. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4354 · Cited by 669
Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa
Khan, K. A., & Kerbel, R. S. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2018.9 · Cited by 670
Deciphering and Reversing Tumor Immune Suppression
Motz, G. T., & Coukos, G. (2013) · Immunity · doi:10.1016/j.immuni.2013.07.005 · Cited by 626
Metadata
- Authors
- Palazón, A., Aragonés, J., Morales-Kastresana, A., de Landázuri, M. O., & Melero, I.
- Affiliations
- Authors' Affiliations: 1Center for Applied Medical Research, University of Navarra, and 2Servicio de Oncología, Clinica Universidad de Navarra, Pamplona, Spain; 3Servicio de Inmunologia, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain
- Hospital Universitario de La Princesa (ES)
- Corresponding author
- Melero, Ignacio
- Venue
- Clinical Cancer Research
- Published
- 2012-03-01
- Volume
- 18
- Issue
- 5
- Pages
- 1207-1213
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2108984461
- Cited by
- 214
- References
- 66
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 13 · 2021: 20 · 2020: 24 · 2019: 8 · 2018: 16 · 2017: 16 · 2016: 24 · 2015: 14 · 2014: 23 · 2013: 16 · 2012: 6
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- tumor hypoxia, hypoxia-inducible factor, HIF-1α, HIF-2α, oxygen sensing, prolyl hydroxylase, asparaginyl hydroxylase, tumor microenvironment, tumor-infiltrating lymphocytes, tumor-associated macrophages, T cell differentiation, tumor angiogenesis, tumor stroma, cancer immunotherapy
- MeSH terms
- Animals, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Signal Transduction, Cell Hypoxia, Lymphocytes, Tumor-Infiltrating, Translational Research, Biomedical
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