Something in the Air: Hyperoxic Conditioning of the Tumor Microenvironment for Enhanced Immunotherapy
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Recent clinical trials in cancer therapy have demonstrated unprecedented responses through blockade of CTLA-4 and PD-1 immune checkpoint pathways. In a provocative recent paper in Science Translational Medicine, Hatfield and colleagues demonstrate the ability of supplemental oxygen to act as a novel immune checkpoint inhibitor by disrupting the hypoxia-adenosine-A2aR pathway.
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High concentrations of oxygen activate the anticancer effects of T cells and NK cells by deactivating the adenosine immunosuppressive microenvironment.
“High concentrations of oxygen activate the anticancer effects of T cells and NK cells by deactivating the adenosine immunosuppressive microenvironment. 127 , 206 , 408”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [408]
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · see citing works
Immune Checkpoint Blockade in Cancer Therapy
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HIF transcription factors, inflammation, and immunity
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Immunological mechanisms of the antitumor effects of supplemental oxygenation
Hatfield, S. M., Kjaergaard, J., Lukashev, D., Schreiber, T. H., Belikoff, B., Abbott, R., Sethumadhavan, S., Philbrook, P., Ko, K., Cannici, R., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa1260 · Cited by 600 · see citing works
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Hypoxia-Induced Inhibition of Adenosine Kinase Potentiates Cardiac Adenosine Release
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Wang, B., Zhao, Q., Zhang, Y., Liu, Z., Zheng, Z., Liu, S., Meng, L., Xin, Y., & Jiang, X. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01820-7 · Cited by 315 · see citing works
Hypoxia signaling in cancer: Implications for therapeutic interventions
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The regulation of immune checkpoints by the hypoxic tumor microenvironment
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Hatfield, S. M., & Sitkovsky, M. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1052934 · Cited by 31 · see citing works
- Authors
- Leone, R. D., Horton, M. R., & Powell, J. D.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Powell, Jonathan D.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 27
- Issue
- 4
- Pages
- 435-436
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4696011
- OpenAlex
- W2058794681
- Cited by
- 42
- References
- 11
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 7 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 7 · 2017: 1 · 2016: 2 · 2015: 2
- FWCI
- 1.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P30CA006973)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- tumor microenvironment, supplemental oxygen, immune checkpoint inhibitors, CTLA-4, PD-1, adenosine receptors, cancer immunotherapy
- MeSH terms
- Animals, Antineoplastic Agents, Female, Humans, Neoplasms, Oxygen
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