Abstract 3405: PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition leads to tumor regression

2020 ◽  
Author(s):  
Joseph M. Gozgit ◽  
Melissa M. Vasbinder ◽  
Ryan P. Abo ◽  
Kaiko Kunii ◽  
Kristy G. Kuplast-Barr ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Type I Interferon ◽  
Tumor Regression ◽  
Interferon Response ◽  
Type I

scholarly journals Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2450
Author(s):  
Aneta Gandalovičová ◽  
Anna-Marie Šůchová ◽  
Vladimír Čermák ◽  
Ladislav Merta ◽  
Daniel Rösel ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Type I Interferon ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Melanoma Cells ◽  
Interferon Response ◽  
Type I ◽  
Expression Of Genes ◽  
Interferon Signalling ◽  
Inflammatory Signalling

The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal–amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.

scholarly journals CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response

Cell Reports ◽  
2017 ◽  
Vol 18 (10) ◽  
pp. 2373-2386 ◽  
Author(s):  
Abdul S. Qadir ◽  
Paolo Ceppi ◽  
Sonia Brockway ◽  
Calvin Law ◽  
Liang Mu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Dependent Type

scholarly journals Inhibiting DDX3X Triggers Tumor-Intrinsic Type I Interferon Response and Enhances Anti-Tumor Immunity

2020 ◽  
Author(s):  
Hyeongjwa Choi ◽  
Juntae Kwon ◽  
Jiafang Sun ◽  
Min Soon Cho ◽  
Yifan Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Rna Binding ◽  
Type I Interferon ◽  
Cytotoxic T Cells ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I

Abstract Accumulating evidence has shown that cellular double-stranded RNAs (dsRNAs) induce antiviral innate immune responses in human normal and malignant cancer cells. However, it is not fully understood how endogenous ‘self’ dsRNA homeostasis is regulated in the cell. Here, we show that an RNA-binding protein, DEAD-box RNA helicase 3X (DDX3X), prevents the aberrant accumulation of cellular dsRNAs. Loss of DDX3X induces dsRNA sensor-mediated type I interferon signaling and innate immune response in breast cancer cells due to abnormal cytoplasmic accumulation of dsRNAs. Dual depletion of DDX3X and a dsRNA-editing protein, ADAR1 synergistically activates the cytosolic dsRNA pathway in the breast cancer cells. Moreover, inhibiting DDX3X enhances the antitumor activity by increasing tumor intrinsic-type I interferon response, antigen presentation, and tumor-infiltration of cytotoxic T cells as well as dendritic cells in breast tumors, which may lead to the development of breast cancer therapy by targeting DDX3X in combination with immune checkpoint blockade.

PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

Cancer Cell ◽  
2021 ◽  
Author(s):  
Joseph M. Gozgit ◽  
Melissa M. Vasbinder ◽  
Ryan P. Abo ◽  
Kaiko Kunii ◽  
Kristy G. Kuplast-Barr ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Antitumor Immunity ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I

scholarly journals Inhibiting DDX3X triggers tumor-intrinsic type I interferon response and enhances anti-tumor immunity

2020 ◽  
Author(s):  
Hyeongjwa Choi ◽  
Juntae Kwon ◽  
Jiafang Sun ◽  
Min Soon Cho ◽  
Yifan Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Rna Binding ◽  
Type I Interferon ◽  
Cytotoxic T Cells ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Interferon Response ◽  
Type I ◽  
Dead Box

ABSTRACTAccumulating evidence has shown that cellular double-stranded RNAs (dsRNAs) induce antiviral innate immune responses in human normal and malignant cancer cells. However, it is not fully understood how endogenous ‘self’ dsRNA homeostasis is regulated in the cell. Here, we show that an RNA-binding protein, DEAD-box RNA helicase 3X (DDX3X), prevents the aberrant accumulation of cellular dsRNAs. Loss of DDX3X induces dsRNA sensor-mediated type I interferon signaling and innate immune response in breast cancer cells due to abnormal cytoplasmic accumulation of dsRNAs. Dual depletion of DDX3X and a dsRNA-editing protein, ADAR1 synergistically activates the cytosolic dsRNA pathway in breast cancer cell. Moreover, inhibiting DDX3X enhances the antitumor activity by increasing tumor intrinsic-type I interferon response, antigen presentation, and tumor-infiltration of cytotoxic T cells as well as dendritic cells in breast tumors, which may lead to the development of breast cancer therapy by targeting DDX3X in combination with immune checkpoint blockade.

Viral Invasion and Type I Interferon Response Characterize the Immunophenotypes during COVID-19 Infection

2020 ◽  
Author(s):  
Lai Wei ◽  
Siqi Ming ◽  
Bin Zou ◽  
Yongjian Wu ◽  
Zhongsi Hong ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Type I

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

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