The role of hypoxiainducible factor 1 in tumor immune evasion
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Date
2021-05-12
Authors
You, Li
Wu, Wenda
Wang, Xu
Fang, Liurong
Adam, Vojtěch
Nepovimová, Eugenie
Wu, Qinghua
Kuča, Kamil
ORCID
0000-0002-8527-286XAdvisor
Referee
Mark
Journal Title
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Volume Title
Publisher
Wiley
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Abstract
Hypoxia-inducible factor 1 (HIF-1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF-1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF-1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF-1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E-2, and programmed death-ligand 1/programmed death-1. Moreover, HIF-1 blocks tumor-associated antigen presentation via major histocompatibility complex class I chain-related/natural killer group 2, member D signaling. Tumor-associated autophagy and the release of tumor-derived exosomes contribute to HIF-1-mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF-1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF-1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF-1 in the regulation of tumor-derived exosomes, as well as the roles of HIF-1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF-1-mediated tumor immune evasion, leading to the development of effective HIF-1-targeting drugs and immunotherapies.
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Citation
MEDICINAL RESEARCH REVIEWS. 2021, vol. 41, issue 3, p. 1622-1643.
https://onlinelibrary.wiley.com/doi/10.1002/med.21771
https://onlinelibrary.wiley.com/doi/10.1002/med.21771
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Peer-reviewed
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Accepted version
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en
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Defence
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(C) Wiley