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Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Open accessAbstract
It is generally accepted that metabolism is able to shape the immune response. Only recently we are gaining awareness that the metabolic crosstalk between different tumor compartments strongly contributes to the harsh tumor microenvironment (TME) and ultimately impairs immune cell fitness and effector functions. The major aims of this review are to provide an overview on the immune system in cancer; to position oxygen shortage and metabolic competition as the ground of a restrictive TME and as important players in the anti-tumor immune response; to define how immunotherapies affect hypoxia/oxygen delivery and the metabolic landscape of the tumor; and vice versa, how oxygen and metabolites within the TME impinge on the success of immunotherapies. By analyzing preclinical and clinical endeavors, we will discuss how a metabolic characterization of the TME can identify novel targets and signatures that could be exploited in combination with standard immunotherapies and can help to predict the benefit of new and traditional immunotherapeutic drugs.
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“Hypoxia, one of the most striking features of the TME, activates multiple signaling pathways that hinder the antitumor effects of various treatments, including immunotherapy. 417”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [417]
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Metadata
- Authors
- Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M.
- Affiliations
- Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, VIB, Leuven, Belgium; Laboratory of Tumor Inflammation and Angiogenesis, Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium; Institute of Anatomy, University of Zurich, Zurich, Switzerland; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal; ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal; Department of Fundamental...
- Ludwig Cancer Research (BE)
- ORCID
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2020-01-01
- Volume
- 100
- Issue
- 1
- Pages
- 1-102
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W2968149989
- Cited by
- 310
- References
- 808
- Citations by year
- 2026: 18 · 2025: 31 · 2024: 69 · 2023: 52 · 2022: 69 · 2021: 56 · 2020: 15
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- IRIS (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- SERVAL (Université de Lausanne) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- EC | European Research Council (773208)
- Fonds Wetenschappelijk Onderzoek (1108919N, G0D1717N, G066515N)
- Stichting Tegen Kanker (2014197)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- tumor microenvironment, tumor hypoxia, cancer metabolism, antitumor immunity, immunotherapy, metabolic crosstalk, oxygen delivery, metabolic competition, predictive biomarkers, combination immunotherapy
- MeSH terms
- Animals, Hypoxia, Humans, Immunity, Immunotherapy, Neoplasms, Tumor Microenvironment
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