Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape
Language English Country Great Britain, England Media electronic
Document type Journal Article, Review, Research Support, Non-U.S. Gov't
Grant support
31972741
Natural Science Foundation of Jilin Province
2016T90477
Postdoctoral Science Foundation of Jiangsu Province
759585
H2020 European Research Council
PubMed
35659268
PubMed Central
PMC9166526
DOI
10.1186/s13045-022-01292-6
PII: 10.1186/s13045-022-01292-6
Knihovny.cz E-resources
- Keywords
- Hypoxia, Hypoxia-inducible factors, Immunotherapy, Personalized medicine, Tumor disease,
- MeSH
- Hypoxia-Inducible Factor 1, alpha Subunit MeSH
- Hypoxia metabolism MeSH
- Immunologic Surveillance MeSH
- Humans MeSH
- Tumor Microenvironment MeSH
- Neoplasms * MeSH
- Tumor Escape * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Hypoxia-Inducible Factor 1, alpha Subunit MeSH
Hypoxia, a common feature of the tumor microenvironment in various types of cancers, weakens cytotoxic T cell function and causes recruitment of regulatory T cells, thereby reducing tumoral immunogenicity. Studies have demonstrated that hypoxia and hypoxia-inducible factors (HIFs) 1 and 2 alpha (HIF1A and HIF2A) are involved in tumor immune escape. Under hypoxia, activation of HIF1A induces a series of signaling events, including through programmed death receptor-1/programmed death ligand-1. Moreover, hypoxia triggers shedding of complex class I chain-associated molecules through nitric oxide signaling impairment to disrupt immune surveillance by natural killer cells. The HIF-1-galactose-3-O-sulfotransferase 1-sulfatide axis enhances tumor immune escape via increased tumor cell-platelet binding. HIF2A upregulates stem cell factor expression to recruit tumor-infiltrating mast cells and increase levels of cytokines interleukin-10 and transforming growth factor-β, resulting in an immunosuppressive tumor microenvironment. Additionally, HIF1A upregulates expression of tumor-associated long noncoding RNAs and suppresses immune cell function, enabling tumor immune escape. Overall, elucidating the underlying mechanisms by which HIFs promote evasion of tumor immune surveillance will allow for targeting HIF in tumor treatment. This review discusses the current knowledge of how hypoxia and HIFs facilitate tumor immune escape, with evidence to date implicating HIF1A as a molecular target in such immune escape. This review provides further insight into the mechanism of tumor immune escape, and strategies for tumor immunotherapy are suggested.
Central European Institute of Technology Brno University of Technology Brno 602 00 Czech Republic
College of Life Science Yangtze University Jingzhou 434025 China
Department of Chemistry and Biochemistry Mendel University in Brno Brno 613 00 Czech Republic
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The role of cellular senescence in neurodegenerative diseases