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897 results for “Therapeutic targets”
Dataset related to article "Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target"
<p>This record contains raw data related to article “Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target"</p> <p>Abstract</p> <p><strong>Background & aims: </strong> The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs).</p> <p><strong>Methods: </strong> We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology.</p> <p><strong>Results: </strong> We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA.</p> <p><strong>Conclusions: </strong> We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA.</p> <p><strong>Lay summary: </strong> Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.</p> <p> </p>
Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target
<p>Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target</p> <p> </p> <p>Abstract</p> <p><strong>Background & aims: </strong>The landscape and function of the immune infiltrate of intrahepatic cholangiocarcinoma (iCCA), a rare, yet aggressive tumor of the biliary tract, remains poorly characterized, limiting development of successful immunotherapies. Herein, we aimed to define the molecular characteristics of tumor-infiltrating leukocytes with a special focus on CD4+ regulatory T cells (Tregs).</p> <p><strong>Methods: </strong>We used high-dimensional single-cell technologies to characterize the T-cell and myeloid compartments of iCCA tissues, comparing these with their tumor-free peritumoral and circulating counterparts. We further used genomics and cellular assays to define the iCCA-specific role of a novel transcription factor, mesenchyme homeobox 1 (MEOX1), in Treg biology.</p> <p><strong>Results: </strong>We found poor infiltration of putative tumor-specific CD39+ CD8+ T cells accompanied by abundant infiltration of hyperactivated CD4+ Tregs. Single-cell RNA-sequencing identified an altered network of transcription factors in iCCA-infiltrating compared to peritumoral T cells, suggesting reduced effector functions by tumor-infiltrating CD8+ T cells and enhanced immunosuppression by CD4+ Tregs. Specifically, we found that expression of MEOX1 was highly enriched in tumor-infiltrating Tregs, and demonstrated that MEOX1 overexpression is sufficient to reprogram circulating Tregs to acquire the transcriptional and epigenetic landscape of tumor-infiltrating Tregs. Accordingly, enrichment of the MEOX1-dependent gene program in Tregs was strongly associated with poor prognosis in a large cohort of patients with iCCA.</p> <p><strong>Conclusions: </strong>We observed abundant infiltration of hyperactivated CD4+ Tregs in iCCA tumors along with reduced CD8+ T-cell effector functions. Interfering with hyperactivated Tregs should be explored as an approach to enhance antitumor immunity in iCCA.</p> <p><strong>Lay summary: </strong>Immune cells have the potential to slow or halt the progression of tumors. However, some tumors, such as intrahepatic cholangiocarcinoma, are associated with very limited immune responses (and infiltration of cancer-targeting immune cells). Herein, we show that a specific population of regulatory T cells (a type of immune cell that actually suppresses the immune response) are hyperactivated in intrahepatic cholangiocarcinoma. Targeting these cells could enable cancer-targeting immune cells to act more effectively and should be looked at as a potential therapeutic approach to this aggressive cancer type.</p> <p> </p>
Pre-clinical spheroid models identify BMX as a therapeutic target for metastatic MYCN non-amplified neuroblastoma
<p>The development of targeted therapies has provided new hope for an increasing number of cancer patients affected by previously incurable diseases. The clinical success of this approach, however, is limited by numerous challenges, including a better control of cell plasticity, particularly in refractory and metastatic patients. Here we addressed this question in Neuroblastoma (NB), an aggressive pediatric malignancy, which remains a clinical challenge for high-risk patients. NB originates from neural crest-derived progenitors through defective differentiation programs combined with oncogenic activity due to genetic and epigenetic alterations. In order to identify critical genes responsible for tumor aggressiveness we performed combined chromatin and transcriptome analyses on matched primary xenografts, spheroids and differentiated adherent cultures, which we derived from metastatic non-<em>MYCN</em> amplified (nMNA) NB patients. Our approach identified the kinase <em>BMX</em> among the most differentially regulated genes between patient-derived xenografts and spheroids versus adherent models. We further found that <em>BMX</em> expression is associated with high tumor stage and poor patient survival in multiple NB transcriptomic datasets and critical to maintain the self-renewal and tumorigenic potential of NB spheroids. Moreover, we uncovered a positive correlation between <em>BMX </em>expression and the mesenchymal tumor cell phenotype, which was previously associated with increased chemo-resistance. Finally, we show that BMX inhibitors can readily reverse this cellular state, increase the sensitivity of NB spheroids toward standard of care chemotherapy, and reduce tumor growth in preclinical NB models. Altogether, our study identifies BMX as a novel promising therapeutic target for high-risk patients with relapsed or refractory nMNA NB tumors.</p>
Comprehensive transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis [RNA-Seq]
GEO Series GSE155301. Mus musculus. 12 samples. Type: Expression profiling by high throughput sequencing.
S100A9 Overexpression Drives Chemoresistance and Poor Prognosis in AML with Adavivint as a Targeted Therapeutic
GEO Series GSE283851. Homo sapiens. 18 samples. Type: Expression profiling by high throughput sequencing.
In vivo CRISPR screening unveils RNA binding protein dependencies for leukemic stem cells and identifies ELAVL1 as a potential therapeutic target [eCLIPseq]
GEO Series GSE127944. Mus musculus. 4 samples. Type: Other.
Transcriptomic Analysis Identifies B-Lymphocyte Kinase as a Therapeutic Target for Desmoplastic Small Round Cell Tumor Cancer Stem Cell-Like Cells [RNA-seq]
GEO Series GSE248761. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Big data-driven target identification by machine learning: DRD2 as a therapeutic target for psoriasis.
GEO Series GSE276511. Mus musculus. 10 samples. Type: Expression profiling by high throughput sequencing.
EZH2 is a potential therapeutic target for H3K27M mutant paediatric gliomas [RNA-Seq mouse tumors]
GEO Series GSE85388. Mus musculus. 4 samples. Type: Expression profiling by high throughput sequencing.
Whole transcriptome sequencing identifies key lncRNAs,circRNAs, and mRNAs for exploring the pathogenesis and therapeutic target of mouse pneumoconiosis
GEO Series GSE246009. Mus musculus. 6 samples. Type: Expression profiling by high throughput sequencing.
Single Cell Profiling of DNMT3A-Mutant Progenitors Novel Pre-Leukemia Marker and Potential Therapeutic Target
GEO Series GSE154624. Mus musculus. 5 samples. Type: Expression profiling by high throughput sequencing.
Steroid sulfatase is a therapeutic target for advanced prostate cancer
GEO Series GSE153245. Homo sapiens. 3 samples. Type: Expression profiling by high throughput sequencing.
Therapeutic Targeting of EZH2 and BET BRD4 in Pediatric Rhabdoid Tumor
GEO Series GSE196058. Homo sapiens. 14 samples. Type: Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing.
RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma
GEO Series GSE253457. Homo sapiens. 12 samples. Type: Expression profiling by array.
Engineered hydrogel reveals contribution of matrix mechanics to esophageal adenocarcinoma and identifies matrix-activated therapeutic targets [RNA-seq]
GEO Series GSE230383. Homo sapiens. 12 samples. Type: Expression profiling by high throughput sequencing.
Whole blood transcriptome analysis reveals SARS-CoV-2 ORF8 as a potential therapeutic and vaccine target
GEO Series GSE155454. Homo sapiens. 58 samples. Type: Expression profiling by high throughput sequencing.
Integrated transcriptomic and in silico drug screening identifies potential stroma-targeting therapeutics in pancreatic cancer
GEO Series GSE196524. Homo sapiens. 48 samples. Type: Expression profiling by array.
Therapeutic targeting of RNA splicing catalysis through inhibition of protein arginine methylation
GEO Series GSE123774. Homo sapiens; Mus musculus. 48 samples. Type: Expression profiling by high throughput sequencing.
Macrophage-derived KIF13B acts as a potential therapeutic target in atherosclerosis by enhancing MERTK-mediated efferocytosis [scRNA-Seq]
GEO Series GSE298574. Mus musculus. 2 samples. Type: Expression profiling by high throughput sequencing.
Gαi1 and Gαi3 Mediate IL-11-Induced Signal Transduction and are Potential Therapeutic Targets for LUAD
GEO Series GSE317274. Homo sapiens. 6 samples. Type: Expression profiling by high throughput sequencing.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.