Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparision of PBMC from PTEN loss and WT glioblastoma patients

ABSTRACT: Glioblastoma (GBM) is a lethal type of brain tumor that is resistant to immunotherapy. Genetic profiling studies have indicated that the tumorigenesis of GBM is linked to somatic genomic alterations in key driver genes, such as TP53, PTEN, CDKN2A, RB1, EGFR, and NF1. These genes regulate critical pathways related to cell growth and resistance to immunotherapy, including the use of immune checkpoint inhibitors (ICIs). One reason for resistance to ICI therapy may be the presence of immunosuppressive myeloid cells, including macrophages and myeloid-derived suppressor cells (MDSCs). We conducted an unbiased analysis to identify specific genetic alterations in GBM cells that may influence MDSC biology and contribute to resistance against immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE286354 | GEO | 2026/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Impact of brequinar treatment on gene expression in bone marrow progenitors of tumor-bearing mice

Project description:Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape in oncology; however, ICIs are effective in subsets of patients. A major limitation of their efficacy is tumor-driven immune suppression, and one key mechanism is the ‘biogenesis’ of myeloid-derived suppressor cells (MDSCs). A fundamental gap in MDSC biology is the dearth of approaches that target their biogenesis. We hypothesized that targeting MDSC biogenesis will mitigate MDSC burden and bolster responses to ICIs. We focused on a class of agents, dihydroorotate dehydrogenase (DHODH) inhibitors, recently found to restore terminal differentiation of leukemic myeloid progenitors and is in clinical trials of AML. One such DHODH inhibitor is brequinar. Using preclinical models of mammary cancer that elicit robust MDSC responses, we demonstrated that brequinar suppressed MDSC biogenesis, enhancing the antitumor and anti-metastatic activity of PD-1-based ICI therapy. In this single-cell RNA transcriptomics study, we sought to determine the impact of brequinar treatment of tumor-bearing mice on altering gene expression in bone marrow myeloid progenitors. Thus, this cutting-edge molecular approach enabled us to test the hypothesis that brequinar acted in the bone marrow at a qualitative level to mitigate MDSC biogenesis.

2022-06-30 | GSE190232 | GEO

Transcriptomic and metabolic effect of immune checkpoint inhibitors on cellular components in renal cell tumor microenvironment and in Sunitinib resistant renal cell carcinoma [III]

Project description:Tumor microenvironmental cellular components like bone marrow cells stromal cells macrophages changes due to sunitinib resistance may affect their efficacy in advanced stage renal cell carcinomas. Immune checkpoint inhibitors (ICIs) have been approved as 2nd line therapy over acquired resistance. Each ICI uniquely affected different cellular components. Better understanding of transcriptomic, metabolomic or proteomic changes due to ICI treatment is necessary to development proper immunotherapy.

2024-03-07 | GSE226968 | GEO

Transcriptomic and metabolic effect of immune checkpoint inhibitors on cellular components in renal cell tumor microenvironment and in Sunitinib resistant renal cell carcinoma [II]

2024-03-07 | GSE226967 | GEO

Transcriptomic and metabolic effect of immune checkpoint inhibitors on cellular components in renal cell tumor microenvironment and in Sunitinib resistant renal cell carcinoma [1]

2024-03-07 | GSE226965 | GEO

Immature monocytic cells within tumors differentiate into immunosuppressive cells in resistant tumors to immunotherapy

Project description:Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced cancers, yet resistance remains a major obsticle. Here, we investigated the role of myeloid cells in shaping the immunosuppressive tumor microenvironment that contributes to ICI resistance. Using mutagenized ICI-sensitive and resistant 4T1 breast cancer clones, we performed single-cell RNA sequencing to characterize immune cell populations post-ICI therapy. We identified monocytic dendritic progenitors (MDPs) and common monocytic progenitors (cMOPs) enriched in sensitive tumors, which may differentiate into immunosuppressive cells in resistant tumors. Analysis of public datasets confirmed the presence of MDP-cMOPs in tumors and blood of breast, lung, and colorectal cancer patients. We found high expression of CXCR4 and IL6R in MDP-cMOPs, and inhibiting these pathways blocked their recruitment and differentiation. Combined targeting of CXCR4 and IL6 pathway with ICI improved responses in resistant tumors, highlighting MDP-cMOPs as contributors to immunotherapy resistance and potential therapeutic targets.

2025-06-05 | GSE298984 | GEO

Entinostat decreases immune suppression to promote an anti-tumor response within a HER2+ breast tumor microenvironment.

Project description:Therapeutic combinations to alter solid tumor microenvironments (TME) in immunosuppressive tumors such as breast cancer are essential to improve their responses to immune checkpoint inhibitors (ICIs). Entinostat, an oral histone deacetylase inhibitor (HDACi), has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown. Here, we employ single-cell RNA-sequencing on HER2 overexpressing breast tumors from mice treated with entinostat and ICIs to characterize for the first time changes across all cell types within the TME. This analysis demonstrates that treatment with entinostat induces a shift from a pro-tumor to an anti-tumor TME signature characterized predominantly by changes in the myeloid cells. We confirm myeloid-derived suppressor cells (MDSCs) within entinostat-treated tumors are associated with a less suppressive G-MDSC phenotype and now demonstrate altered suppressive signaling involves the NFkB and STAT3 pathways. In addition to MDSCs, tumor-associated macrophages are epigenetically reprogrammed toward an anti-tumor M1-like phenotype likely contributing to a more sensitized TME. Overall, our in-depth analysis suggests entinostat-induced changes on multiple myeloid cell types reduce immunosuppression and increase mechanisms of an anti-tumor response that improve sensitivity to ICI. Sensitization of the TME by entinostat could ultimately broaden the population of patients with breast cancer who could derive benefit from ICIs.

2022-01-18 | GSE166321 | GEO

p-FADD-CD8+T cell axis determines hepatocellular carcinoma response to immune checkpoint inhibitors

Project description:The heterogenicity of hepatocellular carcinoma (HCC) remains a key obstacle in turning the majority of ‘immune-cold’ tumors ‘hot’ for effective immune checkpoint inhibitors (ICIs). Through analyzing the naturally-existed ‘hot’ HCC variants, we identified fas-associated death domain (FADD) as a key molecule upregulated in patients with dense tumor-filtrating CD8+T cells and better response to ICIs. Apart from the canonical role in apoptosis pathway, our data showed that CRISPR knockout of hepatoma-intrinsic Fadd led to increased tumor weights in immunocompetent but not immunodeficient mice, accompanied with decreased numbers and IFN-γ/TNF-ɑ production of tumor-filtrating CD8+T cells. Mechanistically, phosphorylated FADD translocated into cell nucleus, where it interacted with Sam68 to upregulate NF-κB transcription of CCL5, thereby promoted CD8+T cell tumor infiltration. Interestingly, anti-PD1 triggered FADD phosphorylation by CD8+T cell-derived IFN-γ/TNF-ɑ in ICI-sensitive, but not resistant tumors. Sequential FADD activation through genetic or pharmacologic approaches to orchestrate p-FADD-CD8+T cell axis therefore overcame ICI resistance in ICI-resistant orthotopic and spontaneous HCC mouse models in vivo. Taken together, our findings may provide insights into the combinatory immunotherapy approaches for the majority of HCC patients in the future.

2025-07-07 | PXD057519 | Pride

A comprehensive gene expression analysis to identify the key regulator suppressing the IFN-γ-inducible factors in tumor cells

Project description:Immune checkpoint inhibitors (ICIs) provide clinical benefits for various advanced malignancies. However, the predictive factors that determine sensitivity to ICIs have not been fully elucidated. To identify the mechanisms underlying ICI resistance, we performed a microarray analysis to compare the IFN-γ-inducible genes between ICI-sensitive AB1-HA and ICI-resistant LLC in vitro.

2024-11-25 | GSE266384 | GEO

Single-Cell RNA Sequencing of Baseline PBMCs Predicts ICI efficacy and irAE Severity in NSCLC Patients

Project description:Immune checkpoint inhibitors (ICIs) have revolutionized by offering remarkable clinical benefits and durable responses for patients with advanced non-small cell lung cancer (NSCLC). However, a very small percentage of patients responded to ICI treatment, and immune-related adverse events (irAEs) leading to treatment discontinuation remain challenges. Despite the recognized need for biomarkers that can predict both the efficacy of ICIs and the risk of irAEs, such biomarkers have yet to be clearly identified. In this study, we performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMC) from NSCLC patients prior to treatment with ICIs. We found that the immune response is generally reduced in patients with poor prognosis. However, the hypoxic environment is particularly more prominent in patients with primary resistance compared to those with acquired resistance. Meanwhile, granzyme and perforin are closely associated with favorable prognosis. We also identified IL1B and CXCL8 as key predictors of irAEs, with their activation linked to inflammation. Moreover, we found that PRF1 in CD8+ T cells and NK cells plays a critical mediator of complete responses and reduced irAE to ICI therapy. These findings deepen our understanding of the mechanisms of ICI efficacy and provide valuable information for optimizing immunotherapy strategies. By identifying biomarkers for both better prognosis and irAEs, this research lays the foundation for personalized immunotherapy approaches that aim to improve clinical outcomes while minimizing the risks associated with ICI treatment.

2025-05-19 | GSE285888 | GEO

Comparing transcriptional profiles of CD14+ monocytes from melanoma patients and healthy donors by scRNA-seq.

Project description:Myeloid-derived suppressor cells (MDSC), a heterogeneous population of myeloid cells, accumulate in the melanoma microenvironment. With the ability to inhibit anti-tumor T cell responses, MDSC have been shown to promote immunosuppression, enhancing tumor progression and tumor cell resistance to the immunotherapy. Novel markers are still needed to define MDSC. In this study,we wanted to find possible markers for M-MDSC by comparing cd14+ monocytes from melanoma patients and healthy donors by scRNA-seq.

2024-07-19 | GSE256291 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data