Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties

ABSTRACT: T cell responses within pediatric brain tumors (PBT) remain poorly understood. We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived brain tumor-infiltrating T cells to map T cell molecular profile with TCR repertoire and clonality. We demonstrate marked clonal expansion of intra-tumoral T cells and reveal their differential phenotype, transcriptional state and functional properties within brain tumors. To understand T cell responses within highly immunogenic tumors that respond to checkpoint blockers, we undertook analysis of human non-small cell lung cancer (NSCLC). We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived lung tumor-infiltrating T cells to map T cell molecular profile with clonality.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221776 | GEO | 2024/01/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single-cell atlas of the developing brain to investigate the cellular origins of pediatric brain tumors

Project description:Gene expression is finely regulated during development, and deregulation can lead to disease. In pediatric brain tumors (PBT), disruption of neurodevelopmental gene regulation programs are suspected to drive oncogenesis. However, the transcriptional landscape and genetic regulation processes of the healthy developing brain are not fully characterized, limiting our investigation of these tumors. We used single-cell RNA-sequencing to generate a transcriptomic atlas of >65,000 cells in the developing forebrain and pons in human and mouse, two regions where PBT commonly arise. We projected bulk RNA-seq profiles for a cohort of 198 PBT onto these cell types, followed by focused analysis of three PBT subtypes by single-cell profiling: WNT medulloblastoma, embryonal tumors with multilayered rosettes (ETMR), and atypical teratoid/rhabdoid tumors (ATRT). Altogether, we pinpoint stalled differentiation during developmental programs as a common etiological mechanism of PBT, providing a valuable resource to aid modeling and therapeutics.

2019-11-19 | GSE133531 | GEO

Evaluating cell culture reliability in pediatric brain tumor primary cells through DNA methylation profiling

Project description:In vitro models of pediatric brain tumors (pBT) are tools instrumental for better understanding the mechanisms contributing to oncogenesis and testing new therapies; and thus, ideally, they should recapitulate the original tumor. We applied DNA methylation (DNAm) and copy number variation (CNV) profiling to characterize 241 pBT samples, including 155 tumors and 86 pBT-derived cell cultures, and considering serum vs serum-free conditions, late vs early passages, and dimensionality (2D vs 3D cultures). We performed a t-SNE classification and identified differentially methylated regions in tumors compared to cell models. Early cell cultures recapitulate the original tumor, but serum media and 2D culturing were demonstrated to significant contribute to the divergence of DNAm profiles from the parental ones. All divergent cells clustered together acquiring a common deregulated epigenetic signature, suggesting a shared selective pressure. In conclusion, DNAm and CNV are informative tools that should be used to assess the recapitulation of pBT-cells from parental tumors.

2024-03-25 | GSE225810 | GEO

Elucidating cellular states of CD8+ T cells regulating anti-tumor response using multi-omic single cell sequencing

Project description:Immune checkpoint blockade (ICB) has led to durable clinical responses in multiple cancer types; however, biomarkers that identify which patients are most likely to respond to ICB are not well defined. Many putative biomarkers developed from a small number of samples often fail to maintain their predictive status in larger validation cohorts. We show across multiple human malignancies and syngeneic murine tumor models that neither pre-treatment T cell receptor (TCR) clonality nor changes in clonality after ICB correlate with response. Dissection of tumor infiltrating lymphocytes pre- and post-ICB by paired single-cell RNA sequencing and single-cell TCR sequencing reveals conserved and distinct transcriptomic features in expanded TCR clonotypes between anti-PD1 responder and non-responder murine tumor models. Overall, our results indicate a productive anti-tumor response is agnostic of TCR clonal expansion. Further, we used single-cell transcriptomics to develop a CD8+ T cell specific gene signature for a productive anti-tumor response and show the response signature to be associated with clinical outcomes to nivolumab monotherapy in CheckMate-067, a phase 3 clinical trial in metastatic melanoma. These results highlight the value of leveraging single-cell assays to dissect heterogeneous tumors and T cell subsets and define cell-type specific transcriptomic biomarkers of ICB response.

2022-07-14 | GSE191129 | GEO

TREM1 deficiency alters the tumor myeloid landscape

Project description:To comprehensively characterize the impact of TREM1 deficiency specifically within the tumor myeloid populations, we selectively enriched the CD45+CD11b+ tumor-infiltrating myeloid cells from tumor-bearing Trem1+/+ and Trem1-/- mice for scRNA-seq analysis.

2023-09-27 | E-MTAB-13246 | biostudies-arrayexpress

The Glioma-Infiltrating T Cell Receptor Repertoire

Project description:While immune signaling has emerged as a defining feature of the glioma microenvironment, local selection of responding T cells and their anti-tumor potential as a population are difficult to measure directly in patients. High-throughput sequencing of T cell receptor repertoires (TCRseq) provides a population-wide statistical description of how T cells respond to disease. Here, we define new immunophenotypes in glioma based on TCRseq and RNA-Seq of tumor tissue, non-neoplastic brain tissue, and peripheral blood from patients. Using information theory, we characterize antigen-driven selection in glioma and its relationship with the expression of distinct immune-functional pathways in the tumor microenvironment. Finally, we identify a strong relationship between usage of certain TCR in peripheral blood and the divergence of the infiltrating T cell population from the peripheral repertoire. We anticipate that these immunophenotypes will be foundational to monitoring and predicting response to anti-glioma vaccines and immunotherapy. We characterized the T cell receptor (TCR) repertoires of 11 high-grade glioma patients, three low-grade glioma patients, and thee non-glioma patients by TCRseq of brain-infiltrating T cells and matching peripheral blood. In addition, we obtained gene expression profiles from brain tissue of each patient by RNA-Seq. We additionally measured the TCR repertoires exclusively from peripheral blood of one additional non-glioma patient.

2016-05-18 | E-GEOD-79338 | biostudies-arrayexpress

Single cell profiling of CD4+ T cells from follicular lymphoma, diffuse large B cell lymphoma and tonsilar samples

Project description:Tumor-infiltrating regulatory T cells contribute to an immunosuppressive tumor microenvironment. We applied single-cell RNA sequencing (scRNA-seq) , TCR sequencing combined with cellular indexing of transcriptomes and epitopes (CITE-seq) on CD4 T cells to decipher the heterogeneity of intratumoral Tregs in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), compared with non-malignant tonsillar tissue.

2023-09-12 | GSE242756 | GEO

IL-2wt and IL-2nα differentially reshape the TME

Project description:Comparing two agonists of interleukin-2 (IL-2), IL-2wt and IL-2nα, differentially reshape the tumor microenvironment (TME). To more comprehensively explore the mechanisms by which the two different IL-2R agonists regulate the TME, we performed single-cell RNA sequencing (scRNA-seq) on immune cells isolated from tumors. We clustered the 18,455 tumor-infiltrating immune cells into 5 populations, and found marked expansion of T cell populations as well as contraction of mononuclear phagocyte populations in both IL-2wt and IL-2nα treated tumors compared with immunoglobulin G (IgG) controls.

2023-04-02 | E-MTAB-12373 | biostudies-arrayexpress

Single-cell atlas of the developing brain to investigate the cellular origins of pediatric brain tumors

Project description:Gene expression is finely regulated during development, and deregulation can lead to disease. In pediatric brain tumors (PBT), disruption of neurodevelopmental gene regulation programs are suspected to drive oncogenesis. However, the transcriptional landscape and genetic regulation processes of the healthy developing brain are not fully characterized, limiting our investigation of these tumors. We used single-cell RNA-sequencing to generate a transcriptomic atlas of the developing forebrain and pons in human and mouse, two regions where PBT commonly arise. We projected bulk RNA-seq profiles for a cohort of 200 PBT onto these cell types, followed by focused analysis of three PBT subtypes by single-cell profiling: WNT medulloblastoma, embryonal tumors with multilayered rosettes (ETMR), and atypical teratoid/rhabdoid tumors (ATRT). In diffuse intrinsic pontine glioma (DIPG), we investigated the effect of removal of the driver H3K27M mutation on differentiation potential using primary tumor-derived cell lines. Altogether, for WNT medulloblastoma, ETMR, and DIPG, we pinpoint stalled differentiation during developmental programs as a common etiological mechanism of these tumors, providing a valuable resource to aid modeling and therapeutics.

| EGAS00001003368 | EGA

scRNA-seq analysis demonstrate alterations in TICs of the TME during TREM1 inhibition and anti-PD-1 treatment in B16F10 melanoma

Project description:To comprehensively characterize the changes within the TME during TREM1 deficiency and anti-PD-1 immune checkpoint blockade therapy, we performed scRNA-seq analysis of the CD45+ TICs in melanoma-bearing C57BL/6 mice receiving the various treatments. We analyzed approximately 8,249 CD45+ cells from the treatment groups with t-SNE analysis, identifying 10 distinct clusters of tumor-infiltrating immune cells

2023-09-27 | E-MTAB-13300 | biostudies-arrayexpress

A clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1

Project description:Tumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. The determination of TM-interconnectivity in individual tumors has been challenging and the impact on patient survival unresolved. Here, a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells has been established using a dye uptake methodology, confirmed with recording of cellular calcium epochs and validated with clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, network connectivity correlated with the mesenchymal subtype and dismal patient survival. CHI3L1 has been identified and validated as a robust molecular marker of connectivity with functional relevance. The connectivity signature allows novel insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients’ prognosis, and serves as a robust prognostic biomarker.

2023-11-27 | PXD044001 | Pride

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