Type I interferon-mediated tumor immunity and its role in immunotherapy

Yu, Renren; Zhu, Bo; Chen, Degao

doi:10.1007/s00018-022-04219-z

Cited by 138 publications

(99 citation statements)

References 171 publications

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“…Mechanistically, tumour-derived HMGB1 induces the production of type I IFNs in dendritic cells via the TLR4-MyD88 pathway, and tumour-derived DNA activates the cGAS/STING pathway to drive the expression of type I IFNs through chaperoning HMGB1, autophagosome, exosome, LL37 or CLEC9A into dendritic cells. 44 Studies also pointed out that IFNα promotes protein ISGylation in a SUMO3dependent manner through TRIM25, and enhanced IFNα-induced holo-ISGylation can also directly protect some proteins from proteasomal degradation. 45 Secondly, miR-2909, known to play a role in immunity and cancer, has been shown to upregulate ISGylation system through STAT1.…”

Section: Discussionmentioning

confidence: 99%

ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma

Zhang

Cui

Cao

et al. 2022

J Cellular Molecular Medi

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Abnormal nuclear structure caused by dysregulation of skeletal proteins is a common phenomenon in tumour cells. However, how skeletal proteins promote tumorigenesis remains uncovered. Here, we revealed the mechanism by which skeletal protein Emerin (EMD) promoted glucose metabolism to induce lung adenocarcinoma (LUAD). Firstly, we identified that EMD was highly expressed and promoted the malignant phenotypes in LUAD. The high expression of EMD might be due to its low level of ubiquitination. Additionally, the ISGylation at lysine 37 of EMD inhibited lysine 36 ubiquitination and upregulated EMD stability. We further explored that EMD could inhibit aerobic oxidation and stimulate glycolysis. Mechanistically, via its β‐catenin interaction domain, EMD bound with PDHA, stimulated serine 293 and 300 phosphorylation and inhibited PDHA expression, facilitated glycolysis of glucose that should enter the aerobic oxidation pathway, and EMD ISGylation was essential for EMD‐PDHA interaction. In clinical LUAD specimens, EMD was negatively associated with PDHA, while positively associated with EMD ISGylation, tumour stage and diameter. In LUAD with higher glucose level, EMD expression and ISGylation were higher. Collectively, EMD was a stimulator for LUAD by inhibiting aerobic oxidation via interacting with PDHA. Restricting cancer‐promoting role of EMD might be helpful for LUAD treatment.

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Section: Discussionmentioning

confidence: 99%

ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma

Zhang

Cui

Cao

et al. 2022

J Cellular Molecular Medi

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“…Type I interferons (IFN-I) are pleotropic cytokines that function in antimicrobial immunity, tumor immunity, and metabolic regulation. However, persistent and unrestrained IFN-I signaling is linked to autoimmune diseases, type I interferonopathies, and organ system failure (Crow and Stetson, 2021; Lei et al, 2021; McNab et al, 2015; Wu et al, 2016; Yu et al, 2022). We recently reported that mtDNA instability and chronic activation of cGAS-STING-IFN-I signaling potentiate age-related tissue pathology in the polymerase gamma (POLG) mutator model of mtDNA disease (Lei et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity

Lei

VanPortfliet

Chen

et al. 2022

Preprint

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Mitochondrial DNA (mtDNA) is a potent agonist of the cyclic GMP-AMP (cGAMP) synthase (cGAS)-Stimulator of Interferon Genes (STING)-type I interferon (IFN-I) pathway. However, the kinetics of mtDNA detection by cGAS or other nucleic acid sensors and the exact immunostimulatory features of mtDNA remain poorly defined. Here, we show that robust and sustained IFN-I responses downstream of mtDNA stress require the nucleic acid sensor Z-DNA binding protein 1 (ZBP1) in a cell death independent manner. Cells experiencing persistent mtDNA release display robust ZBP1 expression, as well as a marked increase in the cytoplasmic pool of cGAS. Biochemical and microscopy analyses reveal that the receptor-interacting protein homotypic interaction motif (RHIMs) of ZBP1 bind the N-terminus of cGAS, leading to its entrapment in the cytoplasm. Moreover, we show that genetic and pharmacologic induction of mtDNA stress leads to the mitochondrial and cytoplasmic accumulation of Z-form DNA. Nuclease treatment or deletion of Z-DNA binding domains of ZBP1 reduces its interaction with cGAS and impairs cGAMP production downstream of mtDNA stress. Finally, we uncover that ZBP1 is a novel regulator of IFN-I-mediated disease pathology, working in tandem with the cGAS-STING pathway to sense mtDNA instability and sustain IFN-I signaling that contributes to cardiac remodeling and heart failure. These results provide new insight into the molecular mechanisms of mtDNA sensing by the innate immune system and reveal that ZBP1 is a cooperative partner for cGAS. Moreover, our findings highlight ZBP1 as a potential therapeutic target in heart failure and other disorders where mtDNA instability drives disease-promoting IFN-I and inflammatory responses.

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“…IFN was discovered by Issacs and Lindenmann in 1957 during their study on phenomenon of virus interference[43], which are classified by type 1, type 2 and type 3. Type 1 IFN is secreted by cells infected with virus and has strong antiviral, antitumor, immunomodulatory properties; Type 2 IFN, secreted by activated T cells, is mainly involved in the immune regulation; Most cells could secrete type 3 IFN, which generate beneficial mucosal immunomodulatory effects[44-46]. Among them, type 1 and type 3 IFN are classical antiviral interferons.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic efficacy of four antiviral drugs in treatment of COVID-19: A protocol for systematic review and Network Meta-analysis

Zhang

et al. 2022

Preprint

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Introduction The COVID-19 pandemic has resulted in a global crisis in public health, however, there are still no safe and effective drugs to resist COVID-19 until now. We will use network meta-analysis to analysis available evidence from RCTs to compare the safety and efficacy of four antiviral drugs (including Ribavirin, Arbidol, Chloroquine Phosphate and Interferon) alone or in combination, in patients with COVID-19 on the basis of standard treatment, to reveal the robustness and strength of evidence for relative efficacy against COVID-19, which will provide better evidence for future clinical decision-making. Methods Using English and Chinese search strategies to search 8 databases including PubMed, Web of Science, Embase, the Cochrane Library, CNKI, CBM, WANFANG Database and VIP. In addition, manual search for references in publications has been supplemented by electronic search. To enhance the effectiveness of this study, only randomized controlled trials of four antiviral drugs (Ribavirin, Arbidol, Chloroquine Phosphate, Interferon) used alone or in combination with the primary therapy shall be included. Analysis The nucleic acid turning negative, complete absorption of lung inflammation, adverse reactions, aggravation and death shall be the primary outcome measures; whereas temperature return to normal, hospitalization, and positive rate after discharge will be the secondary outcomes. To ensure the quality of the systematic evaluation of this study, study screening, data extraction and quality evaluation will be carried out independently by two reviewers, and any differences will be resolved through consultation between them or by a third reviewer. Ethics and dissemination This systematic review will evaluate the efficacy of four antiviral drugs (Ribavirin, Arbidol, Chloroquine Phosphate and Interferon) for Covid-19 in adults. Since all included data will be obtained from published articles, it does not require ethical approval and will be published in a peer-reviewed journal. PROSPERO registration number: CRD42022300104.

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Type I interferon-mediated tumor immunity and its role in immunotherapy

Cited by 138 publications

References 171 publications

ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma

ISGylation of EMD promotes its interaction with PDHA to inhibit aerobic oxidation in lung adenocarcinoma

Cooperative sensing of mitochondrial DNA by ZBP1 and cGAS promotes cardiotoxicity

Therapeutic efficacy of four antiviral drugs in treatment of COVID-19: A protocol for systematic review and Network Meta-analysis

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