Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immuno-Transcriptomic Profiling Identifies Actionable Alterations in Pediatric Solid Malignancies

ABSTRACT: Immuno-Transcriptomic Profiling Identifies Actionable Alterations in Pediatric Solid Malignancies

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Yue Andy Qi

LAB HEAD: Javed Khan, M.D.

PROVIDER: PXD017130 | Pride | 2021-12-07

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20190827_HOS_W632.raw	Raw
	20190827_U2OS_W632.raw	Raw
	20191010_HOS_FLAG.raw	Raw
	20191010_U2OS_FLAG.raw	Raw
	20191105_HOS_W632.raw	Raw

Items per page:

1 - 5 of 10

Publications

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

Brohl Andrew S AS Sindiri Sivasish S Wei Jun S JS Milewski David D Chou Hsien-Chao HC Song Young K YK Wen Xinyu X Kumar Jeetendra J Reardon Hue V HV Mudunuri Uma S US Collins Jack R JR Nagaraj Sushma S Gangalapudi Vineela V Tyagi Manoj M Zhu Yuelin J YJ Masih Katherine E KE Yohe Marielle E ME Shern Jack F JF Qi Yue Y Guha Udayan U Catchpoole Daniel D Orentas Rimas J RJ Kuznetsov Igor B IB Llosa Nicolas J NJ Ligon John A JA Turpin Brian K BK Leino Daniel G DG Iwata Shintaro S Andrulis Irene L IL Wunder Jay S JS Toledo Silvia R C SRC Meltzer Paul S PS Lau Ching C Teicher Beverly A BA Magnan Heather H Ladanyi Marc M Khan Javed J

Cell reports 20211101 8

We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across canc ...[more]

PMID: 34818552

Similar Datasets

Immuno-transcriptomic profiling of extracranial pediatric solid malignancies.

Project description:We perform an immunogenomics analysis utilizing whole-transcriptome sequencing of 657 pediatric extracranial solid cancer samples representing 14 diagnoses, and additionally utilize transcriptomes of 131 pediatric cancer cell lines and 147 normal tissue samples for comparison. We describe patterns of infiltrating immune cells, T cell receptor (TCR) clonal expansion, and translationally relevant immune checkpoints. We find that tumor-infiltrating lymphocytes and TCR counts vary widely across cancer types and within each diagnosis, and notably are significantly predictive of survival in osteosarcoma patients. We identify potential cancer-specific immunotherapeutic targets for adoptive cell therapies including cell-surface proteins, tumor germline antigens, and lineage-specific transcription factors. Using an orthogonal immunopeptidomics approach, we find several potential immunotherapeutic targets in osteosarcoma and Ewing sarcoma and validated PRAME as a bona fide multi-pediatric cancer target. Importantly, this work provides a critical framework for immune targeting of extracranial solid tumors using parallel immuno-transcriptomic and -peptidomic approaches.

| S-EPMC8642810 | biostudies-literature

HLA-B*15:02 peptide presentation in the presence of carbamazepine and related molecules

Project description:Characterisation of peptides presented by the Human Leukocyte Antigen (HLA) class I molecule HLA-B*15:02 in the presence and absence of carbamazepine (CBZ), and related molecules carbamazepine-10,11-epoxide (ECBZ) and oxcarbazepine (OXC).

2021-03-23 | PXD023545 | Pride

The potential of PARP as a therapeutic target across pediatric solid malignancies.

Project description:BackgroundPediatric cancer is the leading cause of disease-related death in children and the need for better therapeutic options remains urgent. Due to the limited number of patients, target and drug development for pediatrics is often supplemented by data from studies focused on adult cancers. Recent evidence shows that pediatric cancers possess different vulnerabilities that should be explored independently from adult cancers.MethodsUsing the publicly available Genomics of Drug Sensitivity in Cancer database, we explore therapeutic targets and biomarkers specific to the pediatric solid malignancies Ewing sarcoma, medulloblastoma, neuroblastoma, osteosarcoma, and rhabdomyosarcoma. Results are validated using cell viability assays and high-throughput drug screens are used to identify synergistic combinations.ResultsUsing published drug screening data, PARP is identified as a drug target of interest across multiple different pediatric malignancies. We validate these findings, and we show that efficacy can be improved when combined with conventional chemotherapeutics, namely topoisomerase inhibitors. Additionally, using gene set enrichment analysis, we identify ribosome biogenesis as a potential biomarker for PARP inhibition in pediatric cancer cell lines.ConclusionCollectively, our results provide evidence to support the further development of PARP inhibition and the combination with TOP1 inhibition as a therapeutic approach in solid pediatric malignancies. Additionally, we propose ribosome biogenesis as a component to PARP inhibitor sensitivity that should be further investigated to help maximize the potential utility of PARP inhibition and combinations across pediatric solid malignancies.

| S-EPMC10077757 | biostudies-literature

Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.

Project description:Targeted kinase inhibitors and camptothecins have shown preclinical and clinical activity in several cancers. This trial evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities of sorafenib and topotecan administered orally in pediatric patients with relapsed solid tumors. Sorafenib was administered twice daily and topotecan once daily on days 1-5 and 8-12 of each 28-day course. The study utilized a standard 3 + 3 dose escalation design. Three dose levels (DL) were evaluated: (1) sorafenib 150 mg/m(2) and topotecan 1 mg/m(2) ; (2) sorafenib 150 mg/m(2) and topotecan 1.4 mg/m(2) ; and (3) sorafenib 200 mg/m(2) and topotecan 1.4 mg/m(2) . Pharmacokinetics were ascertained and treatment response assessed. Thirteen patients were enrolled. DL2 was the determined MTD. Grade 4 thrombocytopenia delaying therapy for >7 days was observed in one of six patients on DL2, and grade 4 neutropenia that delayed therapy in two of three patients on DL3. A patient with preexisting cardiac failure controlled with medication developed a transient drop in the left ventricular ejection fraction that improved when sorafenib was withheld. Sorafenib exposure with or without topotecan was comparable, and the concentration-time profiles for topotecan alone and in combination with sorafenib were similar. One objective response was noted in a patient with fibromatosis. We determined MTD to be sorafenib 150 mg/m(2) twice daily orally on days 1-28 combined with topotecan 1.4 mg/m(2) once daily on days 1-5 and 8-12. While these doses are 1 DL below the MTD of the agents individually, pharmacokinetic studies suggested adequate drug exposure without drug interactions. The combination had limited activity in the population studied.

| S-EPMC4735769 | biostudies-literature

Influenza B-derived peptide presentation by HLA-B*07:02, -B*08:01 and -B*35:01

Project description:Analysis of peptide presentation by Human Leukocyte Antigen (HLA) class I of influenza B infected C1R cells expressing HLA-B*07:02, -B*08:01 or -B*35:01.

2024-03-04 | PXD045000 | Pride

Gastrointestinal malignancies harbor actionable MET exon 14 deletions.

Project description:Recently, MET exon 14 deletion (METex14del) has been postulated to be one potential mechanism for MET protein overexpression. We screened for the presence of METex14del transcript by multiplexed fusion transcript analysis using nCounter assay followed by confirmation with quantitative reverse transcription PCR with correlation to MET protein expression by immunohistochemistry (IHC) and MET amplification by fluorescence in situ hybridization (FISH). We extracted RNAs from 230 patients enrolled onto the prospective molecular profiling clinical trial (NEXT-1) (NCT02141152) between November 2013 and August 2014. Thirteen METex14del cases were identified including 3 gastric cancer, 4 colon cancer, 5 non-small cell lung cancer, and one adenocarcinoma of unknown primary. Of these 13 METex14del cases, 11 were MET IHC 3+ and 2 were 2+. Only one out of the 13 METex14del cases was MET amplified (MET/CEP ratio > 2.0). Growths of two (gastric, colon) METex14del+ patient tumor derived cell lines were profoundly inhibited by both MET tyrosine kinase inhibitors and a monoclonal antibody targeting MET. In conclusion, METex14del is a unique molecular aberration present in gastrointestinal (GI) malignancies corresponding with overexpression of MET protein but rarely with MET amplification. Substantial growth inhibition of METex14del+ patient tumor derived cell lines by several MET targeting drugs strongly suggests METex14del is a potential actionable driver mutation in GI malignancies.

| S-EPMC4695055 | biostudies-literature

Influenza-derived peptide presentation by HLA-A*11:01

Project description:Analysis of the immunopeptidome of Human Leukocyte Antigen (HLA)-A*11:01 during influenza infection. Analyses were performed using the Class I reduced C1R cell line transfected with the HLA class I allele HLA-A*11:01.

2022-02-15 | PXD028985 | Pride

HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

Project description:Autoimmune diseases are often associated with HLA molecules. Multiple sclerosis (MS) is a prototypical example with the HLA-DR15 haplotype as strongest genetic factor. How it contributes to MS is not clear, but key to understand this and other autoimmune diseases. Autoreactive CD4+ T cells and proinflammatory B cells are central pathogenetic factors, and since HLA-DR molecules present peptides to CD4+ T cells, we characterized the peptidomes of the two HLA-DR15 allomorphs DR2a and DR2b on B cells. Self-peptides from HLA-DR α- and β-chains themselves are abundantly presented on B cells. We identified autoreactive CD4+ T cell clones, which recognize HLA-DR-derived self-peptides and peptides from the MS-related infectious agents EBV and Akkermansia and the autoantigen RAS guanyl-releasing protein 2. Our data demonstrate how the two MS-associated HLA-DR15 allomorphs function as antigen-presenting structures and source of peptides during peripheral maintenance of autoreactive T cells and activation by MS-associated pathogens.

2020-10-22 | PXD015249 | Pride

DDA acquisition of the immunopeptidomes of C1R-B*57:01 and C1R-A*02:01 cell lines

Project description:Immunopeptidomes are the peptide repertoires bound by the molecules encoded by the major histocompatibility complex (MHC) (human leukocyte antigen (HLA) in humans). These HLA-peptide complexes are presented on the cell surface for immune T cell recognition. Immunopeptidomics utilizes tandem mass spectrometry (MS/MS) to identify and quantify peptides bound to HLA molecules. The dataset deposited here contains the DDA runs used to generate the spectral libraries of the HLA-bound peptides purified and isolated from C1R-B*57:01 and C1R-A*02:01 cell lines.

2023-02-13 | PXD034429 | Pride

Pediatric haematopoiesis and related malignancies.

Project description:Survival after acute paediatric (0-14 years), adolescent (15-19 years) and young adult (20-39 years) leukaemia has improved substantially over the last five decades, particularly for acute lymphoblastic leukaemia (ALL) and acute promyelocytic leukaemia. This progress represents one of the most successful achievements in the history of medicine and has been attributed to the development of effective chemotherapy regimens, improvement in supportive care, better risk stratification, use of targeted therapies, and advances in haematopoietic stem cell transplantation. Recent studies have revealed improvement in survival over time for all age groups and subtypes of leukaemia. However, these outcomes varied widely by age and are associated with sociodemographic and clinical factors. The present review concludes that survival and early death after acute leukaemia has greatly improved among young patients. However, inequalities in outcomes remain and are likely a result of multiple factors.

| S-EPMC5494839 | biostudies-other

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