Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA177120 | ENA |
REPOSITORIES: ENA
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Project description:Interferons are pro-inflammatory cytokines that promote immune cell engagement to eliminate malignant cells. Paradoxically, interferon signaling can also activate anti-inflammatory16 mechanisms that allow cancer cells to evade the immune system. We sought to determine how chronic interferon affects cancer cell metabolism and whether these changes contribute to a switch from anti-tumorigenic to pro-tumorigenic interfon activity. We found that chronic type II interferon (IFN-II) exposure uniquely affected mitochondrial electron transport chain activity,20 rewired the TCA cycle, and upregulated eicosanoid production. Furthermore, it caused a type I interferon (IFN-I) response mediated by mitochondrial RNA release that synergized with IFN-II to enhance tumor growth via increased immunosuppressive prostaglandin E₂ synthesis. This covert IFN-prostaglandin pathway could be an actionable therapeutic target to reduce tumor growth24 and/or combat immunotherapy resistance.
2026-09-01 | GSE307168 | GEO
Project description:Interferons are pro-inflammatory cytokines that promote immune cell engagement to eliminate malignant cells. Paradoxically, interferon signaling can also activate anti-inflammatory16 mechanisms that allow cancer cells to evade the immune system. We sought to determine how chronic interferon affects cancer cell metabolism and whether these changes contribute to a switch from anti-tumorigenic to pro-tumorigenic interfon activity. We found that chronic type II interferon (IFN-II) exposure uniquely affected mitochondrial electron transport chain activity,20 rewired the TCA cycle, and upregulated eicosanoid production. Furthermore, it caused a type I interferon (IFN-I) response mediated by mitochondrial RNA release that synergized with IFN-II to enhance tumor growth via increased immunosuppressive prostaglandin E₂ synthesis. This covert IFN-prostaglandin pathway could be an actionable therapeutic target to reduce tumor growth24 and/or combat immunotherapy resistance.
2026-09-01 | GSE307167 | GEO
Project description:Interferons are pro-inflammatory cytokines that promote immune cell engagement to eliminate malignant cells. Paradoxically, interferon signaling can also activate anti-inflammatory16 mechanisms that allow cancer cells to evade the immune system. We sought to determine how chronic interferon affects cancer cell metabolism and whether these changes contribute to a switch from anti-tumorigenic to pro-tumorigenic interfon activity. We found that chronic type II interferon (IFN-II) exposure uniquely affected mitochondrial electron transport chain activity,20 rewired the TCA cycle, and upregulated eicosanoid production. Furthermore, it caused a type I interferon (IFN-I) response mediated by mitochondrial RNA release that synergized with IFN-II to enhance tumor growth via increased immunosuppressive prostaglandin E₂ synthesis. This covert IFN-prostaglandin pathway could be an actionable therapeutic target to reduce tumor growth24 and/or combat immunotherapy resistance.
2026-09-01 | GSE307166 | GEO
Project description:IFNs are highly pleiotropic cytokines also endowed with marked anti-angiogenic activity. In this study, the mRNA expression profiles of endothelial cells (EC) exposed in vitro to IFN-alpha, IFN-beta, or; IFN-gamma were determined. We found that in HUVEC as well as in other EC types 175 genes were upregulated (>2-fold increase) by IFNs, including genes involved in the host response to RNA viruses, inflammation, and apoptosis. Interestingly, 41 genes showed a >5-fold higher induction by IFN-alpha in EC compared to human fibroblasts; among them, the gene encoding the angiostatic chemokine CXCL11 was selectively induced by IFN-alpha in EC along with other genes associated; with angiogenesis regulation, including CXCL10, TRAIL, and guanylate binding protein 1 (GBP-1). These transcriptional changes were confirmed and extended by quantitative PCR analysis and ELISA; whereas IFN-alpha and IFN-beta exerted virtually identical effects on transcriptome modulation, a differential gene regulation by type I and type II IFN emerged, especially as far as quantitative aspects were concerned. In vivo, IFN-alpha-producing tumors over-expressed murine CXCL10-11,; GBP-1 and TRAIL, with evidence of CXCL11 production by tumor-associated EC. Overall, these findings improve our understanding of the anti-angiogenic effects of IFNs by showing that these cytokines trigger an anti-angiogenic transcriptional program in EC. Moreover, we suggest that quantitative differences in the magnitude of the transcriptional activation of IFNresponsive genes could form the basis for cell-specific transcriptional signatures. In press, J. Immunol. 2007. Experiment Overall Design: comparison of interferon effects on endothelial cells (HUVEC, HMVEC) and fibrobloasts
2009-04-08 | E-GEOD-3920 | biostudies-arrayexpress
Project description:The activation of RIG-I-like receptor (RLR) signaling in cancer cells is widely recognized as a critical cancer therapy method. The expected mechanism of RLR ligand-mediated cancer therapy involves the promotion of cancer cell death and strong induction of interferon (IFN)-β that affects the tumor microenvironment. We have recently shown that activation of RLR signaling in triple-negative breast cancer cells (TNBC) attenuates TGF-β signaling, which partly contributes to the promotion of cancer cell pyroptosis. However, the consequences of suppression of TGF-β signaling by RLR ligands with respect to IFN-β-mediated tumor suppression are not well characterized. This study showed that cytosolic induction of a typical RLR ligand polyI:C in cancer cells produces significant levels of IFN-β, which inhibits the growth of the surrounding cancer cells. In addition, IFN-β-induced cell cycle arrest in surrounding cancer cells was inhibited by the expression of constitutively active Smad3 (caSmad3). caSmad3 suppresses IFN-β expression through the alleviation of IRF3 binding to the canonical target genes, as suggested by ChIP-seq analysis. Based on these findings, a new facet of the pro-tumorigenic function of TGF-β that suppresses IFN-β expression is suggested when exploiting RLR-mediated cancer treatment in TNBC.
2021-12-16 | GSE188457 | GEO
Project description:The activation of RIG-I-like receptor (RLR) signaling in cancer cells is widely recognized as a critical cancer therapy method. The expected mechanism of RLR ligand-mediated cancer therapy involves the promotion of cancer cell death and strong induction of interferon (IFN)-β that affects the tumor microenvironment. We have recently shown that activation of RLR signaling in triple-negative breast cancer cells (TNBC) attenuates TGF-β signaling, which partly contributes to the promotion of cancer cell pyroptosis. However, the consequences of suppression of TGF-β signaling by RLR ligands with respect to IFN-β-mediated tumor suppression are not well characterized. This study showed that cytosolic induction of a typical RLR ligand polyI:C in cancer cells produces significant levels of IFN-β, which inhibits the growth of the surrounding cancer cells. In addition, IFN-β-induced cell cycle arrest in surrounding cancer cells was inhibited by the expression of constitutively active Smad3 (caSmad3). caSmad3 suppresses IFN-β expression through the alleviation of IRF3 binding to the canonical target genes, as suggested by ChIP-seq analysis. Based on these findings, a new facet of the pro-tumorigenic function of TGF-β that suppresses IFN-β expression is suggested when exploiting RLR-mediated cancer treatment in TNBC.
2021-12-16 | GSE178830 | GEO
Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). An ISG-targeted CRISPR screen using IFN beta-treated U-2 OS cells was performed to determine which ISGs were required in order for host cells to suppress Venezuelan equine encephalitis virus (VEEV) infection.
2023-05-26 | GSE233196 | GEO
Project description:Host cells produce interferon (IFN) in response to viral infections. Secreted interferon results in the transcription and production of hundreds of interferon-stimulated genes (ISGs). A genome-wide CRISPR screen using IFN beta-treated U-2 OS cells was performed to determine which ISGs were required in order for host cells to suppress Venezuelan equine encephalitis virus (VEEV) infection.
2023-05-26 | GSE233195 | GEO
Project description:Type I interferon (IFN-α/β) is the first line of defense against viral infection. Mouse models have been pivotal to our understanding of IFN-α/β in immunity, although validation of these findings in humans has not been possible. We investigated a previously healthy child with fatal susceptibility to the live-attenuated measles, mumps and rubella (MMR) vaccine. By targeted resequencing we identified a homozygous mutation in the high-affinity interferon-α/β receptor (IFNAR2), which rendered cells unresponsive to IFN-α/β and led to unrestricted replication of IFN-attenuated viruses. Reconstitution of patient cells with wild-type IFNAR2 restored IFN-α/β responsiveness and viral resistance. Despite the failure to control vaccine viruses, the patient showed no evidence of susceptibility to conventional viral pathogens in vivo and adaptive immunity appeared normal. Human IFNAR2 deficiency therefore reveals an essential role for IFN-α/β in resistance to attenuated viruses, but significant and unexpected redundancy overall in antiviral immunity. Total RNA isolated from IFNAR2-deficient patient (in triplicate) and control (three independent control lines) fibroblasts treated with IFNalpha, IFNbeta or IFNgamma (1000 IU/mL) for 10h
2015-06-12 | E-GEOD-67737 | biostudies-arrayexpress
Project description:Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables to individually monitor the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment.
2013-10-10 | GSE41477 | GEO