Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Vorinostat treatment of PPS-ICBR cells

ABSTRACT: We generated immune checkpoint blockade resistant cell lines from a prostate tumor driven by Probasin-Cre Pten/P53/Smad4 loxp deletion, through serial implantation and ICB treatment. We then wanted to explore whether gene expression changes associated with resistance to immune checkpoint blockade could be reversed by treating ICB resistant cells with the pan-HDAC inhibitor Vorinostat. We used a microarray to determine gene expression changes caused by Vorinostat treatment in these cells with biological duplicates.

ORGANISM(S): Mus musculus Mus

PROVIDER: GSE205469 | GEO | 2024/02/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Combining anti-PD1 and vorinostat improves anti-tumor treatment in IDH-mutant brain tumors

Project description:Enhancer RNA (eRNA) is critical element with highly specific pattern in regulatory network across infiltrated immune cells. Herein we developed eRNA immunotherapy signature (eRIS) based on these eRNAs which significantly connected with anti-tumor immune cells. The eRIS was highly correlated with objective response rate (ORR) to immune checkpoint blockade (ICB) treatment, and was significantly increased in these patients who benefit from ICB treatment. By integrating with pharmacogenomics datasets, we screened hundreds of eRIS associated anti-cancer drugs, which showed potential in improving immunotherapy with cancer type or subtype-specific specific manner. We further characterized one drug, the HDAC inhibitor vorinostat, in isocitrate dehydrogenase mutant gliomas, and found Combining vorinostat with anti-PD-1 could decrease tumor size and increase survival time in vivo by enhancing abundance of anti-tumor immune cells. We further provided eRIS markers which showed strong capacity of eRIS in predicting immunotherapy response in clinical samples or animal models. Our study revealed the potential utility of eRIS to improve immunotherapy response by identifying combinational drugs, that provide novel insights to benefit patients in certain cancer or subtypes.

2024-05-01 | GSE248513 | GEO

Immunologic and clinical activity to ICB combinations in DAPPER Leiomyosarcoma cohort

Project description:Non-inflamed (cold) tumors such as leiomyosarcoma (LMS) do not benefit from immune checkpoint blockade (ICB) monotherapy. Combining ICB with angiogenesis-, or poly-ADP ribose polymerase (PARP) inhibitors may increase tumor immunogenicity by altering the immune cell composition of the tumor microenvironment (TME). The DAPPER phase II study evaluated the safety, immunologic, and clinical activity of ICB-based combinations in pre-treated LMS patients.

2024-01-01 | E-MTAB-12922 | biostudies-arrayexpress

Vorinostat treatment of PPS-ICBR cells

Project description:Vorinostat treatment of PPS-ICBR cells

| PRJNA845791 | ENA

RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of potential vorinostat-resistance candidate genes

2014-07-07 | GSE56788 | GEO

Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance

Project description:Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK pY18 phosphorylation and spontaneous activation of CD8+ and CD4+ T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1/pY18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, (R)-9b, recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.

2023-03-11 | PXD037546 | Pride

A ketogenic diet can revert acquired resistance to immunotherapy in prostate cancer through β-hydroxybutyrate-mediated inhibition of histone deacetylases

Project description:Prostate cancer is the second leading cause of cancer deaths in men in the US. In the past decade, immune checkpoint blockade (ICB) drugs targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) have revolutionized the field of cancer therapeutics, but the objective response rate in prostate cancers is in the low single digits. A major complicating issue is that immunotherapies can have significant adverse effects, so there is a clinical need for novel combinatorial strategies that do not involve additional or compounding adverse effects. We developed a model system of advanced prostate cancer that has acquired resistance to ICB therapy. The PD-1 resistant sublines showed strong downregulation of the mouse major histocompatibility complex (MHC-I), which was reversed by treating cells with either the pan-histone deacetylase (HDAC) inhibitor Vorinostat or β-hydroxybutyrate. When mice bearing these ICB resistant tumor are treated with either Vorinostat, with a cyclical ketogenic diet (CKD), or with a 1,3-butanediol diet (BD), tumors are resensitized to ICB therapy. We analyzed changes in the tumor immune microenvironment and showed that this effect is driven by a shift in monocyte differentiation, changing from M2 polarized immunosuppressive macrophages into iNOS+ dendritic cells instead. This differentiation is dependent on an ICB-induced increase in CD40L+ CD8+ T-cells in the tumor immune microenvironment. Our results indicate a novel mechanism in which a ketogenic diet can be used to increase therapeutic efficacy of ICB therapy.

2024-02-13 | GSE206561 | GEO

RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of potential vorinostat-resistance candidate genes

Project description:Potential vorinostat-resistance candidate genes were identified using RNA interference screening in vorinostat-resistant HCT116 cells (HCT116-VR) using a synthetic lethal approach. In order to understand the mechanisms by which these genes contributed to vorinostat response, transcriptomic analysis was conducted on HCT116-VR cells and those with siRNA-mediated knockdown of each of the vorinostat resistance candidate genes. There are 45 samples in total, from triplicate independent biological experiments of 15 samples each. The negative control to which all gene knockdowns are compared is the mock transfection control (mock).

2014-07-07 | E-GEOD-56788 | biostudies-arrayexpress

RNA-seq analysis of isogenic mouse prostate cancer cell lines with distinct sensitivity to immune checkpoint therapy

Project description:Resistant to immune checkpoint blockade (ICB) therapy, especially in a few solid tumor types including advanced prostate cancer (PCa), represents a formidable clinical challenge. In this study, we developed a series of ICB-resistant PCa cell lines from an ICB-sensitive PCa cell line previously developed from the PB-Cre+ PtenL/L p53L/L Smad4L/L mouse model of metastatic PCa. These four cell lines were profiled with RNAseq.

2024-02-13 | GSE252986 | GEO

RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of GLI1 or PSMD13 with or without vorinostat treatment

Project description:Transcriptome analysis was conducted on vorinostat resistant HCT116 cells (HCT116-VR) upon knockdown of potential vorinostat resistance candidate genes in the presence and absence of vorinostat. Potential vorinostat resistance candidate genes chosen for this study were GLI1 and PSMD13, which were identified through a genome-wide synthetic lethal RNA interference screen. To understand the transcriptional events underpinning the effect of GLI1 and PSMD13 knockdown (sensitisation to vorinostat-induced apoptosis), cells were first subjected to gene knockdown, then to treatment with vorinsotat or the solvent control. Two timepoints for drug treatment were assessed: a timepoint before induction of apoptosis (4hrs for siGLI1 and 8hrs for siPSMD13) and a timepoint when apoptosis could be detected (8hrs for siGLI1 and 12hrs for siPSMD13). There are 42 samples in total, from triplicate independent biological experiments of 14 samples each.

2016-06-30 | E-GEOD-57871 | biostudies-arrayexpress

RNA-seq analysis of vorinostat-resistant HCT116 cells following gene knockdown of GLI1 or PSMD13 with or without vorinostat treatment

2016-06-30 | GSE57871 | GEO