Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis

Shi, Lewis Zhichang; Bonner, James A.

doi:10.3390/ijms222212295

Cited by 20 publications

(16 citation statements)

References 155 publications

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“…The most well-understood metabolic changes that occur during cancer progression include alterations in the PI3K/AKT/mTOR pathway, stabilization of HIF-1α, and enhanced expression of MYC genes ( 3 – 5 ). Recent data support the role of IFNs in regulating cancer metabolism; for example, IFNs can activate the JAK/STAT signaling pathway in cancer cells to regulate metabolic processes and activate a tumor immune response ( 6 ). However, the role of IFN-stimulated genes (ISGs) in metabolic reprogramming is not fully understood.…”

Section: Metabolic Reprogramming Makes Cancer Cells More Lethalmentioning

confidence: 95%

The rise of viperin: the emerging role of viperin in cancer progression

Weinstein¹,

Godet²,

Gilkes³

2022

Journal of Clinical Investigation

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Viperin, an IFN-regulated gene product, is known to inhibit fatty acid β-oxidation in the mitochondria, which enhances glycolysis and lipogenesis during viral infections. Yet, its role in altering the phenotype of cancer cells has not been established. In this issue of the JCI , Choi, Kim, and co-authors report on a role of viperin in regulating metabolic alterations in cancer cells. The authors showed a correlation between clinical outcomes and viperin expression levels in multiple cancer tissues and proposed that viperin expression was upregulated in the tumor microenvironment via the JAK/STAT and PI3K/AKT/mTOR/HIF-1α pathways. Functionally, viperin increased lipogenesis and glycolysis in cancer cells by inhibiting fatty acid β-oxidation. Viperin expression also enhanced cancer stem cell properties, ultimately promoting tumor initiation in murine models. This study proposes a protumorigenic role for viperin and identifies HIF-1α as a transcription factor that increases viperin expression under serum starvation and hypoxia.

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Section: Metabolic Reprogramming Makes Cancer Cells More Lethalmentioning

confidence: 95%

The rise of viperin: the emerging role of viperin in cancer progression

Weinstein¹,

Godet²,

Gilkes³

2022

Journal of Clinical Investigation

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“…JAK-STAT signaling is a vital downstream pathway of IFN receptors that stimulates IFN-stimulated gene (ISG) production ( 8 , 105 ). The JAK family comprises of JAK1-3 and TYK2.…”

Section: Role Of Hbx In the Jak-stat Pathwaymentioning

confidence: 99%

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

et al. 2022

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As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

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“…JAK/STAT consists of three components: the tyrosine kinase receptor receiving the signal, the tyrosine kinase transmitting the signal-JAK, and the transcription factor producing the effect-STAT [ 43 , 44 ]. As the downstream pathway of IFN receptors, the JAK/STAT signaling must respond rapidly to initiate ISG production [ 45 ].…”

Section: Activation Of Innate Immune and Inflammatory Response By Hep...mentioning

confidence: 99%

Innate Immunity, Inflammation, and Intervention in HBV Infection

Yang¹,

Wan²,

Zhang

et al. 2022

Viruses

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Hepatitis B virus (HBV) infection is still one of the most dangerous viral illnesses. HBV infects around 257 million individuals worldwide. Hepatitis B in many individuals ultimately develops hepatocellular carcinoma (HCC), which is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. The innate immunity acts as the first line of defense against HBV infection through activating antiviral genes. Along with the immune responses, pro-inflammatory cytokines are triggered to enhance the antiviral responses, but this may result in acute or chronic liver inflammation, especially when the clearance of virus is unsuccessful. To a degree, the host innate immune and inflammatory responses dominate the HBV infection and liver pathogenesis. Thus, it is crucial to figure out the signaling pathways involved in the activation of antiviral factors and inflammatory cytokines. Here, we review the interplay between HBV and the signal pathways that mediates innate immune responses and inflammation. In addition, we summarize current therapeutic strategies for HBV infection via modulating innate immunity or inflammation. Characterizing the mechanisms that underlie these HBV-host interplays might provide new approaches for the cure of chronic HBV infection.

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Bridging Radiotherapy to Immunotherapy: The IFN–JAK–STAT Axis

Cited by 20 publications

References 155 publications

The rise of viperin: the emerging role of viperin in cancer progression

The rise of viperin: the emerging role of viperin in cancer progression

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection

Innate Immunity, Inflammation, and Intervention in HBV Infection

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