Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NF-κB- and TET2-mediated macrophage reprogramming overrides the anti-inflammatory effects of hypoxia and improves responses in human cancer (DNA methylation II).

ABSTRACT: Macrophages orchestrate various aspects of immunity and tissue homeostasis in health and disease. In cancer, the presence of macrophages is largely associated with poor prognosis, due to their reprogramming into immunosuppressive cells in the tumor microenvironment (TME). In this study, we investigated the effects of hypoxia, a key feature of the TME, on the functional, epigenetic, and transcriptional status of macrophages. Surprisingly, we found that hypoxia boosts the immunogenicity of macrophages in vitro, in a process that is partially regulated by DNA methylation. Specifically, we find a cluster of pro-inflammatory genes that undergo DNA demethylation and transcriptional upregulation during macrophage activation in hypoxia. These genes are regulated by NF-κB, while HIF1α contributes to the transcriptional program through DNA methylation-independent mechanisms. In cancers such as bladder and ovarian carcinomas, the signatures of hypoxic inflammatory macrophages are found in immune-rich tumors, where they correlate with better patient prognoses. The NF-κB-associated DNA hypomethylation is recapitulated in an in vivo-equivalent subset of hypoxic inflammatory macrophages, isolated from ovarian tumors, validating the translation of the in vitro results. Functionally, co-culture assays and putative cell-cell communication analyses suggest that hypoxic-activated macrophages enhance T cell-mediated responses. Our results challenge existing paradigms regarding the effects of hypoxia on macrophages and highlight novel target cells to ameliorate cancer responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261318 | GEO | 2024/10/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

NF-κB- and TET2-mediated macrophage reprogramming overrides the anti-inflammatory effects of hypoxia and improves responses in human cancer ChIP-Seq).

Project description:Macrophages orchestrate various aspects of immunity and tissue homeostasis in health and disease. In cancer, the presence of macrophages is largely associated with poor prognosis, due to their reprogramming into immunosuppressive cells in the tumor microenvironment (TME). In this study, we investigated the effects of hypoxia, a key feature of the TME, on the functional, epigenetic, and transcriptional status of macrophages. Surprisingly, we found that hypoxia boosts the immunogenicity of macrophages in vitro, in a process that is partially regulated by DNA methylation. Specifically, we find a cluster of pro-inflammatory genes that undergo DNA demethylation and transcriptional upregulation during macrophage activation in hypoxia. These genes are regulated by NF-κB, while HIF1α contributes to the transcriptional program through DNA methylation-independent mechanisms. In cancers such as bladder and ovarian carcinomas, the signatures of hypoxic inflammatory macrophages are found in immune-rich tumors, where they correlate with better patient prognoses. The NF-κB-associated DNA hypomethylation is recapitulated in an in vivo-equivalent subset of hypoxic inflammatory macrophages, isolated from ovarian tumors, validating the translation of the in vitro results. Functionally, co-culture assays and putative cell-cell communication analyses suggest that hypoxic-activated macrophages enhance T cell-mediated responses. Our results challenge existing paradigms regarding the effects of hypoxia on macrophages and highlight novel target cells to ameliorate cancer responses.

2024-10-09 | GSE261321 | GEO

NF-κB- and TET2-mediated macrophage reprogramming overrides the anti-inflammatory effects of hypoxia and improves responses in human cancer (DNA methylation I).

2024-10-09 | GSE261317 | GEO

NF-κB- and TET2-mediated macrophage reprogramming overrides the anti-inflammatory effects of hypoxia and improves responses in human cancer (RNA-Seq II).

2024-10-09 | GSE261323 | GEO

NF-κB- and TET2-mediated macrophage reprogramming overrides the anti-inflammatory effects of hypoxia and improves responses in human cancer (RNA-Seq I).

2024-10-09 | GSE261322 | GEO

Secreted factors from M1 macrophages drive prostate cancer stem cell plasticity by upregulating NANOG, SOX2 and CD44 through NFκB signaling [LNCaP]

Project description:The inflammatory tumor microenvironment (TME) is a key driver of tumor-promoting processes. Tumor-associated macrophages are one of the main immune cell types in the TME and their density increases during cancer progression. Here, we investigated the influence of pro-inflammatory (M1) and immunosuppressive (M2) macrophages on prostate cancer lineage plasticity. Our findings reveal that M1 macrophage secreted factors upregulate genes related to stemness while downregulating genes associated with androgen response in LNCaP prostate cancer cells. Cancer stem cell plasticity markers NANOG, KLF4, SOX2, OCT4 and CD44 were stimulated by the secreted factors from M1 macrophages. Moreover, AR and its target gene KLK3 were observed to be suppressed in LNCaP cells treated exposed to secreted factors from M1 macrophages. Inhibition of NF-κB signaling using the IKK16 inhibitor resulted in downregulation of NANOG, SOX2 and CD44. Our study highlights that the secreted factors from M1 macrophages drive prostate cancer cell plasticity by upregulating the expression of cancer stem cell plasticity markers through NF-κB signaling pathway.

2024-08-21 | GSE251851 | GEO

Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses

Project description:Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified up-regulated DCLK1 in macrophages in atherosclerotic lesions of ApoE-/- mice fed an HFD and determined that macrophage-specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL-induced inflammation via NF-κB signaling pathway in primary macrophages. Co-immunoprecipitation followed by LC-MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF-κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF-κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis.

2023-02-27 | PXD039083 | Pride

SHISA3 reprograms tumor-associated macrophages toward an M1 phenotype and enhances cancer immunotherapy

Project description:The main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2-like tumor-associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, we found that the transmembrane protein SHISA3 is induced by DAMPs/PAMPs in macrophages via nuclear factor-κB (NF-κB) transcription factors, and SHISA3 forms complex with HSPA8 to reciprocally activates NF-κB signaling thus maintains M1 polarization of macrophages. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8+ T cell-mediated antitumor immunity. Local delivery of mRNA encoding Shisa3 enables therapy of cancer by dual effects on tumor cells and TAMs, and enhance the efficacy of PD-1 antibody. Taken together, our findings describe the role of SHISA3 in reprogramming TAMs that ameliorates cancer immunotherapy To find new molecules that regulate macrophage polarization, we performed transcriptomic analysis on early macrophages polarization induced by LPS for 0, 2, 4 hours.

2024-10-02 | GSE255711 | GEO

A pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics

Project description:Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. RNA profiles of wild type (WT) MEFs treated with TNF-alpha were generated by deep sequencing using Illumina GAIIx. Examination of H3K4me3 histome modification in MEF.

2013-08-05 | E-GEOD-47494 | biostudies-arrayexpress

Gene expression profiling of side population (SP) cells and non-SP cells in Hodgkin Lymphoma (HL) cell lines_2

Project description:SP cells in HL cell lines are characterized by up-regulation of genes related to TNF-alpha Signaling via NF-κB, Inflammatory Response and Hypoxia compared to the non-SP cells.

2021-06-28 | GSE142413 | GEO

Gene expression profiling of side population (SP) cells and non-SP cells in Hodgkin Lymphoma (HL) cell lines_1

2021-06-28 | GSE142411 | GEO