The TNFSF12/TWEAK modulates colonic inflammatory fibroblast differentiation and promotes fibroblast-monocyte interactions
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA996920 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25367465_1.fastq.gz | Fastqsanger.gz | |||
| SRR25367465_2.fastq.gz | Fastqsanger.gz | |||
| SRR25367466_1.fastq.gz | Fastqsanger.gz | |||
| SRR25367466_2.fastq.gz | Fastqsanger.gz | |||
| SRR25367467_1.fastq.gz | Fastqsanger.gz |
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Project description:Fibroblasts acquire a pro-inflammatory phenotype in inflammatory bowel disease (IBD), but the factors driving this process and how fibroblasts contribute to the immune response is incompletely understood. The TNF superfamily factor 12 (TWEAK) has gained interest as a mediator of chronic inflammation. Here, we explore its role as a driver of inflammatory responses in fibroblasts and its contribution to fibroblast-monocyte interaction using human primary colonic fibroblasts, THP1 and peripheral blood mononuclear cells (PBMC). TWEAK induced the expression of cytokines, chemokines and immune receptors in fibroblasts. The TWEAK up-regulated transcriptome shared 29% homology with the previously published transcriptional profile of inflammatory fibroblasts from ulcerative colitis. TWEAK elevated surface expression of activated fibroblasts markers and adhesion molecules (PDPN, ICAM-1 and VCAM-1) and secretion of IL-6, CCL2 and CXCL10. In co-culture, fibroblasts induced monocyte adhesion and promoted a CD14high/ICAM-1 high phenotype in THP1 cells, both of which were enhanced when fibroblasts were pre-stimulated with TWEAK. Medium from TWEAK-treated fibroblast-THP1 co-cultures had elevated levels of CXCL1 and IL-8. PBMCs in co-culture with TWEAK-treated fibroblasts had altered surface expression of CCR2 and CD16, and increased CXCL1 and CXCL10. Our results indicate that TWEAK promotes and inflammatory fibroblast-monocyte crosstalk that may be amenable for therapeutic intervention.
2024-04-23 | GSE237845 | GEO
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. U2OS cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
2013-10-04 | E-GEOD-41828 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. Pan02 cells untreated or treated with 1090-TW (TWEAK) for 4 hours, 8 hours, or 24 hours. Four replicates for each condition were performed.
2013-10-04 | E-GEOD-42047 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. ACHN cells untreated or treated with 1090-TW (TWEAK) for 4 hours, 8 hours, or 24 hours. Four replicates for each condition were performed.
2013-10-04 | E-GEOD-42046 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. MDA-MB-436 cells untreated or treated with 1090-TW (TWEAK) for 15 minutes, 1 hour, 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
2013-10-04 | E-GEOD-42045 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. CAKI cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212) or Vehicle for 24 hours. Four replicates for each condition were performed. RNA was extracted from xenografts, processed and hybridized to human and mouse chips.
2013-10-04 | E-GEOD-42049 | biostudies-arrayexpress
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration. ACHN cells impanted as xenografts in Athymic, Nu/Nu nude mice, treated with anti-TWEAK antibody (TW212), B20 antibody control or Vehicle for 4 hours, 8 hours, or 24 hours. Five replicates for each condition were performed.
2013-10-04 | E-GEOD-42048 | biostudies-arrayexpress
Project description:Cholangiocarcinoma is a cancer of the hepatic bile ducts that is typically detected at a stage too advanced for resection. Additionally, chemotherapy is of limited efficacy, hence, novel therapeutic approaches are urgently required, including targeting of the cancer stroma. A macrophage-derived signal, tumour necrosis factor-like weak inducer of apoptosis (TWEAK), binds to cell-surface fibroblast growth factor-inducible 14 (Fn14), on cholangiocarcinoma cells to induce cytokine and chemokine expression and secretion. These TWEAK-inducible factors from cholangiocarcinoma cells can also affect macrophage polarisation. We characterised proteins secreted by four well-characterised human cholangiocarcinoma cell lines in the presence or absence of recombinant human TWEAK (100 ng/ml), to discover novel TWEAK-inducible factors that could drive pro-tumour niche formation.
| MSV000084273 | MassIVE
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
2013-10-04 | GSE42047 | GEO
Project description:Tumor necrosis factor-related weak inducer of apoptosis, TWEAK, is a TNF superfamily member that mediates signaling through its receptor fibroblast growth factor inducible-14, Fn14. In tumor cell lines, TWEAK induces proliferation, survival and NF-kappaB signaling and gene expression that promote tumor growth and suppress antitumor immune responses. Anti-TWEAK antibody, RG7212, inhibits tumor growth in vivo with decreases in pathway activation markers and modulation of tumor, blood and spleen immune cell composition. Candidate response prediction markers, including Fn14, have been identified in mouse models. Phase I pharmacodynamic data from patients are consistent with preclinical results. TWEAK:Fn14 signaling is upregulated in human cancer and pathway activation induces tumor proliferation and survival signaling. Blockade with anti-TWEAK mAb, RG7212, inhibits tumor growth in multiple models in mice. TWEAK induces changes that suppress anti-tumor immune responses and RG7212 blocks these effects resulting in changes in tumor immune cell composition and decreases in cytokines that promote immunosuppression. Antitumor efficacy in mice was observed in a range of Fn14 expressing models with pathway activation and expressing either wild-type or mutant p53, BRAF or KRAS suggesting both a patient selection strategy and potential broad clinical applicability. Preclinical mechanism of action hypotheses are supported by Phase I clinical data, with decreases in proliferation markers and increased tumor T cell infiltration.
2013-10-04 | GSE42046 | GEO