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Hypoxia-inducible factors and innate immunity in liver cancer
Vincent Wai-Hin Yuen, Carmen Chak-Lui Wong
Vincent Wai-Hin Yuen, Carmen Chak-Lui Wong
Published August 4, 2020
Citation Information: J Clin Invest. 2020;130(10):5052-5062. https://doi.org/10.1172/JCI137553.
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Review Series

Hypoxia-inducible factors and innate immunity in liver cancer

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Abstract

The liver has strong innate immunity to counteract pathogens from the gastrointestinal tract. During the development of liver cancer, which is typically driven by chronic inflammation, the composition and biological roles of the innate immune cells are extensively altered. Hypoxia is a common finding in all stages of liver cancer development. Hypoxia drives the stabilization of hypoxia-inducible factors (HIFs), which act as central regulators to dampen the innate immunity of liver cancer. HIF signaling in innate immune cells and liver cancer cells together favors the recruitment and maintenance of pro-tumorigenic immune cells and the inhibition of anti-tumorigenic immune cells, promoting immune evasion. HIFs represent attractive therapeutic targets to inhibit the formation of an immunosuppressive microenvironment and growth of liver cancer.

Authors

Vincent Wai-Hin Yuen, Carmen Chak-Lui Wong

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Figure 2

Roles of the hypoxia/HIF signaling pathway in innate immune cells in HCC.

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Roles of the hypoxia/HIF signaling pathway in innate immune cells in HCC...
(A) In the presence of O2, the HIF-1/2α subunit is hydroxylated by the PHD enzymes at two specific proline residues, enabling the binding of VHL. VHL targets the hydroxylated HIF-1/2α subunit for ubiquitin-mediated proteasomal degradation. (B) In the absence of O2, the HIF-1/2α subunit is stabilized and dimerizes with HIF-1β, together with cotranscriptional factors p300 and CBP, to drive the transcription of genes encompassing hypoxia-responsive elements (HREs). (C) The hypoxia/HIF signaling pathway in the innate immune cells directly affects their properties in HCC.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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