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SRP173390
Homo sapiens
38 Downloadable Samples
Illumina HiSeq 2500
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: CD4+ T helper cells were sorted as naive T cells (CD4+CD25-CD45RA+), Treg (CD4+CD25+IL7Rlo), Th1 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6-), Th2 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6-), Th17 (CD4+CD25-IL7RhiCD45RA-CXCR3-CCR6+), Th1-17 (CD4+CD25-IL7RhiCD45RA-CXCR3+CCR6+), and Tfh subsets (CXCR5+ counterparts of each). RNA-seq cDNA library construction was performed using the SMART-Seq v4 Ultra Low Input RNA Kit (Clontech) with 2?ng of input RNA. Sequencing libraries were prepared using the Nextera XT DNA Library Prep Kit (Illumina).
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
Description
Immunotherapies that block inhibitory checkpoint receptors on T cells have transformed the clinical care of cancer patients. However, the clonal origin of tumor-specific T cells following checkpoint blockade in patients remains unclear. Here, we performed paired single-cell RNA- and T cell receptor (TCR)- sequencing on site-matched tumors from patients with basal cell carcinoma (BCC) pre- and post-anti-PD-1 therapy. Tracking TCR clonotypes and transcriptome phenotypes revealed a coupling of tumor-recognition, clonal expansion, and T cell dysfunction: the response to treatment was accompanied by a clonal expansion of CD8+CD39+ T cells, which co-expressed markers of chronic T cell activation and exhaustion. However, this response was not accompanied by an expansion of pre-existing tumor-specific T cell clonotypes; rather, expanded T cell clones post-therapy comprised novel clonotypes, which were not previously observed in the same tumor. Clonal replacement of T cells was preferentially observed in tumor-specific exhausted CD8+ T cells, compared to other distinct T cell phenotypes, and was more evident in patients who exhibited a clinical response to treatment. These results, enabled by single-cell multi-omic profiling of clinical samples, demonstrate that the chronic activation of pre-existing tumor-infiltrating T cells may limit their re-invigoration following checkpoint blockade, and that a successful response relies on the expansion of a distinct repertoire of tumor-specific T cell clones. Overall design: Dissociated tumor samples were sorted as either CD45+ CD3+ tumor-infiltrating T cells, other CD45+ CD3- tumor-infiltrating lymphocytes and CD45- CD3- tumor/stromal cells. Sorted cells were subjected to paired single cell RNA- and TCR-sequencing on the droplet based 10X Genomics platform.
Publication Title
Clonal replacement of tumor-specific T cells following PD-1 blockade.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 147 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed and paraffin-embedded (FFPE) biopsies has many unique challenges. Here we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers from diagnostic prostate needle core biopsies.
Publication Title
Application of a Clinical Whole-Transcriptome Assay for Staging and Prognosis of Prostate Cancer Diagnosed in Needle Core Biopsy Specimens.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease which exhibits selective motor neuron death caused by a ubiquitous deficiency of the survival motor neuron (SMN) protein. It remains unclear how the ubiquitous reduction of SMN lead to death in selective motor neuron pools. Medial motor neuron columns (MMC) are vulnerable, whereas lateral motor columns (LMC) are resistant to motor neuron death in SMA. Here we performed microarray and pathway analysis comparing cholera toxin subunit B (CTb) labeled vulnerable MMC and resistant LMC of pre-symptomatic SMA with corresponding motor neuron columns of control mice to identify pathways involved in selective motor neuron death in SMA. WT is FVB. SMN is Delta7 (SMN7;SMN2;Smn-) on a FVB background.
Publication Title
Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 365 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The objective of this study is to: 1) Characterize the innate immune responsiveness of patients with inborn errors in Toll-IL1 receptor signaling pathway (IRAK4, MyD88 deficiencies) compared to healthy subjects, through the analysis of blood leukocytes' transcriptional profiles after stimulation with ligands for the whole set of Toll-like receptors and IL-1Rs plus whole bacteria. 2) Understand the redundancies in TLR pathway in humans. 3) Explore the use of blood profiling approaches to assess the immune status of an individual by using Primary Immune Deficiencies as a proof of principle.
Publication Title
A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4.
Sample Metadata Fields
Sex, Race
View Samples- Homo sapiens
- 693 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 621 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The objective of this study is to: 1) Characterize the immune responsiveness to administration of non-live vaccines in three cohorts of healthy adult subjects through the analysis of blood leukocytes transcriptional profiles. 2) Validate whole blood transcriptional profiles generated from standard 3mL blood draws versus 200uL blood draws obtained by finger stick. 3) Discover potential biomarkers for immune-responsiveness to non-live vaccines.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The objective of this study is to: 1) Characterize the cellular origin of transciptional signatures observed on day 1 after vaccination with 2009/10 seasonal influenza and pneumococcal vaccine discovered by transcriptional profiling of whole blood samples in data set WholeBlood_SysVax. 2) Discover potential biomarkers for immune-responsiveness to non-live vaccines.
Publication Title
Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
The excessive perchlorate utilization as an oxidizer in rocket propellants and blasting agents had led to the contamination of surface and ground waters. This chemical is known to compete with iodine for binding to the thyroid membrane receptors potentially causing hypothyroidism and fetal retardation in pregnant women. Nevertheless, to date, its biological effects are not completely understood. We have investigated the molecular mechanisms responsive to perchlorate in the nematode C. elegans to nominate a candidate gene for further peruse in the development of a C.elegans perchlorate biosensor. Perchlorate (1 mg/mL) affected the transcriptional response of Regulation of developmental process, growth, defense mechanisms and stress response, among other biological processes.
Publication Title
Perchlorate detection <i>via</i> an invertebrate biosensor.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Publication Title
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Sample Metadata Fields
Cell line
View Samples