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Single cell Transcriptomic analysis of CD8+ T cells treated with anti-CD137 agonists within VK12653 Multiple Myeloma bone marrow microenvironment .

ABSTRACT: We report the single cell RNA sequencing of mouse CD8+ T cells infiltrating VK12653 Multiple Myeloma lesions upon treatment with anti-CD137 agonists .

ORGANISM(S): Mus musculus

PROVIDER: GSE205702 | GEO | 2023/06/30

REPOSITORIES: GEO

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Transcriptomic analysis of VK12653 Multiple Myeloma bone marrow microenvironmentupon treatment with anti-CD137 agonists

Project description:We report the RNA sequencing of VK12653 Multiple Myeloma bone marrow microenvironment upon treatment with anti-CD137 agonists

2023-06-30 | GSE206545 | GEO

Gene expression patterns of tumor-infiltrating CD8 T cells according to the CD137 expression in human metastatic ovarian cancer

Project description:We report the differences of gene expression pattern of tumor-infiltrating CD8 T cells between CD137 expressing cells and CD137 non-expressing cells in human metastatic ovarian cancer. Samples are obtained from 3 ovarian cancer patients, and we sorted CD137 expressing cells and CD137 non-expressing cells in CD39 expressing CD8 T cells for RNA sequencing. We found that even though the CD39 expression and PD-1 expression levels are similar, CD137 expressing cells showed more activated and less exhausted phenotypes than CD137 non-expressing cells.

2020-05-12 | GSE150301 | GEO

Differentiated agonistic antibody targeting CD137 eradicates large tumors without hepatotoxicity

Project description:CD137 (4-1BB) is a member of the TNFR superfamily that represents a promising target for cancer immunotherapy. Recent insights into the function of TNFR agonist antibodies implicate epitope, affinity, and IgG subclass as critical features, and these observations help explain the limited activity and toxicity seen with clinically tested CD137 agonists. Here we describe the preclinical characterization of CTX-471, a fully human IgG4 agonist of CD137 that engages a unique epitope that is shared by human, cynomolgus monkey, and mouse and is associated with a differentiated pharmacology and toxicology profile. In vitro, CTX-471 increased IFN-γ production by human T cells in an FcγR-dependent manner, displaying an intermediate level of activity between two clinical-stage anti-CD137 antibodies. In mice, CTX-471 exhibited curative monotherapy activity in various syngeneic tumor models and showed a unique ability to cure mice of very large (~500 mm3) tumors compared to validated antibodies against checkpoints and TNFR superfamily members. Extremely high doses of CTX-471 were well-tolerated, with no signs of hepatic toxicity. Collectively, these data demonstrate that CTX-471 is a unique CD137 agonist that display an excellent safety profile and an unprecedented level of monotherapy efficacy against very large tumors.

2020-01-30 | GSE144473 | GEO

Multiple myeloma

Project description:Multiple myeloma

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Binding of STAT5 upon IL-2 treatment to genomic sites in mouse CD8 T cells costimulated in vivo through CD134 plus CD137

Project description:OT-I CD8 T cells primed with cognate SIINFEKL peptide and agonists to the costimulatory receptors CD134 and CD137 were stimulated with and without IL-2, and then STAT5 ChIP-seq was performed.

2015-09-30 | GSE72565 | GEO

CD137-CIS IO

Project description:CD137 cis-costimulation is superior to trans-costimulation at inducing transcriptomic differences in T-cell proliferation and DNA repair programs We used microarrays to detail differentially expressed genes of cis- and trans CD137-costimulated CD8 T cells with respect to CD3-TCR stimulation

2021-09-28 | GSE158041 | GEO

CD137-CIS IO

Project description:CD137-CIS IO

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Microarray analysis of a multiple myeloma cell line, MM1S, treated with adenosine A2A and Beta-2 Adrenergic Receptor agonists in combination with dexamethasone

Project description:We have used an agnostic approach to identify drug combinations by using combination high throughput screening (cHTS) technology and make the surprising discovery that adenosine A2A and beta-2 adrenergic receptor agonists are highly synergistic, selective and novel agents that enhance glucocorticoid activity in B-cell malignancies. We used the microarray study to understand the synergistic mechanism between dexamethasone and A2A receptor agonist or Beta-2 Adrenergic receptor agonist in a multiple myeloma cell line, MM1S.

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Microarray analysis of a multiple myeloma cell line, MM1S, treated with adenosine A2A and Beta-2 Adrenergic Receptor agonists in combination with dexamethasone

2012-03-31 | E-GEOD-30644 | biostudies-arrayexpress

Multiple myeloma-derived extracellular vesicles modulate the bone marrow immune microenvironment

Project description:One of the hallmarks of multiple myeloma (MM) is a permissive BM microenvironment. Increasing evidence suggest that cell-to-cell communication between myeloma and immune cells via tumor cell-derived extracellular vesicles (EV) plays a key role in the pathogenesis of MM. Hence, we aimed to explore BM immune alterations induced by MM-derived EV. For this, we inoculated immunocompetent BALB/cByJ mice with a myeloma cell line - MOPC315.BM -, inducing a MM phenotype. Upon tumor establishment, characterization of the BM microenvironment revealed the expression of both activation and suppressive markers by lymphocytes, such as Granzyme b and PD-1, respectively. In addition, conditioning of the animals with MOPC315.BM-derived EV, before transplantation of the MOPC315.BM tumor cells, did not anticipate the disease phenotype. However, it induced features of suppression in the BM milieu, such as an increase in PD-1 expression by CD4+ T cells. Overall, our findings reveal the involvement of MOPC315.BM-derived EV protein content as promoters of immune niche remodeling, strengthening the importance of assessing the mechanisms by which MM may impact the immune microenvironment.

2022-07-05 | PXD032934 | Pride

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