Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene Expression Profiling of human T cells: Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo

ABSTRACT: Transcriptome analysis of human peripheral blood T cells Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic (changes in gene-expression profile) andfunctional signatures in vivo in purified human T cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE77714 | GEO | 2016/02/10

SECONDARY ACCESSION(S): PRJNA311270

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene Expression Profiling of human monocytes: Combination Therapy with AntiâCTLA-4 and AntiâPD-1 Leads to Distinct Immunologic Changes In Vivo

Project description:Transcriptome analysis of human peripheral blood monocytes Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic (changes in gene-expression profile) and functional signatures in vivo in purified human T cells and monocytes. RNA extracted from freshly isolated monocytes from peripheral blood of patients treated with either antiâPD-1 (n = 6), antiâCTLA-4 (n = 5), Combo therapy with antiâPD-1 and antiâCTLA-4 concurrently (Combo, n = 6), and Seq antiâPD-1 in patients with prior antiâCTLA-4 (Seq, n = 3) was analyzed using the Affymetrix GeneChip Human Transcriptome 2.0 exon array. No techinical replicates were performed.

2016-02-16 | E-GEOD-77924 | biostudies-arrayexpress

Gene Expression Profiling of human T cells: Combination Therapy with Antiâ??CTLA-4 and Antiâ??PD-1 Leads to Distinct Immunologic Changes In Vivo

Project description:Transcriptome analysis of human peripheral blood T cells Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic (changes in gene-expression profile) andfunctional signatures in vivo in purified human T cells. RNA extracted from freshly isolated T cells from peripheral blood of patients treated with either antiâ??PD-1 (n = 6), antiâ??CTLA-4 (n = 5), Combo therapy with antiâ??PD-1 and antiâ??CTLA-4 concurrently (Combo, n = 6), and Seq antiâ??PD-1 in patients with prior antiâ??CTLA-4 (Seq, n = 3) was analyzed using the Affymetrix GeneChip Human Transcriptome 2.0 exon array. No techinical replicates were performed.

2016-02-10 | E-GEOD-77714 | biostudies-arrayexpress

Gene Expression Profiling of human monocytes: Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo

2016-02-16 | GSE77924 | GEO

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade [WES]

Project description:Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms.

2017-08-10 | GSE100808 | GEO

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade [RNA-seq]

2017-08-10 | GSE100807 | GEO

RNAseq of tumor samples from CT26 syngeneic mouse treated with a PD-L1 and CTLA-4 immunotherapy combination

Project description:The ability to modulate immune-inhibitory pathways using checkpoint blockade antibodies such as PD-1, PD-L1, and CTLA-4 represents a significant breakthrough in cancer therapy in recent years. This has driven interest in identifying small-molecule-immunotherapy combinations to increase the proportion of responses. Murine syngeneic models, which have a functional immune system, represent an essential tool for pre-clinical evaluation of new immunotherapies. However, immune response varies widely between models and the translational relevance of each model is not fully understood, making selection of an appropriate pre-clinical model for drug target validation challenging. Utilizing RNAseq transcriptomic profiling, we have characterised the changes in gene regulatory pathways and immune populations in CT26 mice after treatment with the combination of anti-PD-L1 and anti-CTLA-4 antibodies. At day 7 post tumor implant, the pathways analysis of differentially expressed genes indicated an enrichment for migration of leukocytes in response to inflammation and communication between innate and adaptive immune cells. Similarly, analysis of upstream regulators suggested that lipopolysaccharide, IL-1B, TNF, IFNG, and NFKB1A pathways associated with inflammation were activated. At day 14, pathways related T-helper cell signalling pathways were upregulated. In addition, upstream regulators of the lipopolysaccharide and IFNG pathway, as well STAT1 and IL21 pathway were enriched, indicative of innate and adaptive immune response to inflammation.

2020-04-16 | E-MTAB-7777 | biostudies-arrayexpress

Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD1 Therapy (scRNA-seq)

Project description:Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the PD1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti-CTLA-4 when combined with anti-PD1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels, and when combined with dual CTLA-4/PD1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+T cells were necessary for the therapeutic benefit because the efficacy was compromised when CD8+ T cells were depleted. Expression of Cxcr3 on CD8+ T cells is necessary and sufficient since CD8+ T cells from Cxcr3+/+ but not Cxcr3–/– mice rescued efficacy in T cell‒deficient mice. Finally, rational scheduling of anti-CTLA-4 “priming” with chemotherapy followed by anti-PD1 therapy achieved equivalent efficacy with reduced overall drug exposure. These data suggest that this combination approach should be clinically tested to overcome resistance to current therapies in ICC patients.

2024-01-18 | GSE253627 | GEO

Intratumoral anti-CTLA-4 delivery by an oncolytic Vaccinia virotherapy virus elicits CD8+ T cell immunity and synergizes with anti-PD-1 to reject “cold” tumors

Project description:CTLA-4 is a clinically validated antibody target for cancer immunotherapy. Toxicity, which is linked to efficacy in available anti-CTLA-4 regimens has, however, restricted their use and precluded full therapeutic dosing. Here we describe and preclinically characterize a potentially safe and highly efficacious strategy to target CTLA-4. Intratumoral administration of an oncolytic Vaccinia virus, engineered to encode a novel Treg depleting, checkpoint-blocking, anti-CTLA-4 antibody and GM-CSF (VVGM-aCTLA4) achieved tumor-restricted CTLA-4 receptor saturation and Treg-depletion, and regressed diverse tumors spanning inflamed to immunologically ignorant microenvironments. Critically, intratumorally “ignited” antitumor immunity translated into stronger systemic expansion of tumor-specific CD8+ T cells compared with systemic anti-CTLA-4. In a clinically relevant mouse model resistant to systemic immune checkpoint blockade, i.t. VVGM-aCTLA4 synergized with anti-PD-1 to reject “cold” tumors. Based on our established proof-of-concept, a clinical trial evaluating i.t. VVGM-aCTLA4 (BT-001) alone and in combination with anti-PD-1 in metastatic or advanced solid tumors has commenced.

2022-02-08 | GSE176052 | GEO

Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti-PD1 Therapy (bulk RNA-seq)

2024-01-15 | GSE253275 | GEO

Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking

Project description:Intracranial B16 melanoma tumors isolated from C57Bl6 mice were analyzed by mRNAseq. Four experimental groups were analyzed: (1) Mice with intracranial tumors receiving IgG; (2) Mice with intracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy; (3) Mice with intracranial plus extracranial tumors receiving IgG; (4) Mice with intracranial plus extracranial tumors receiving anti-PD-1 plus anti-CTLA-4 therapy. Taggart et al., PNAS 2018;

2018-02-01 | GSE109485 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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