Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of gammadelta T cells infiltrating human colon adenocarcinomas

ABSTRACT: gd T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor Vd usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed gd T cell profiling in colon tumours, comprising mRNA quantification using the Nanostring platform, in combination with mass and flow cytometry and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vd1Vd2 cells. Nanostring analyses of flow cytometry sorted Vd1, Vd2 and non-Vd1Vd2 cells showed a large variation in gd T cell subsets between individual tumours, and we suggest that individual gd T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266504 | GEO | 2024/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of cultured Vd1 and Vd2 gd T cells following non-TCR agonist stimulation

Project description:The two major human gd T cell subsets, Vd1 and Vd2, display differences in tissue tropism and agonist responses, but we have little insight into global differences that may exist at the gene expression level. This is due to the small numbers of these cells that can be obtained from healthy donors, which limit comprehensive, comparative gene expression analyses. We established a culture method that expands Vd1 and Vd2 cells from the same PBL preparation to levels sufficient for sorting and microarray analysis. Although the subsets were expanded identically (anti-TCR mAb, plus IL-15), 392 and 614 genes were identified, which were differentially expressed in the two subsets, from two donors, respectively. Approximately 4,500 genes changed in both subsets following PMA/ionomycin treatment; about 50% of these genes were subset-specific. Both subsets responded to a crude LPS preparation, but only 6% of the responsive genes were the same. The differentially expressed genes were consistent with Vd2 cells being more inflammatory and Vd1 cells having more of a regulatory phenotype. Both subsets expressed transcripts encoding an array of innate and NK cell receptors, supporting the relationship of gd?T cells to the innate immune system. Our results show that circulating Vd1 and Vd2 subsets in humans have considerable, inherent differences in gene expression following treatment with non-TCR agonists, supporting unique functional roles for these cells in vivo.

2007-11-08 | E-GEOD-3720 | biostudies-arrayexpress

Comparison of Vdelta1 and Vdelta2 cells

Project description:Gene expression analysis comparison of ex vivo isolated GD T cell subpopulations Under non-pathological conditions, human gd T cells represent a small fraction of CD3+ T cells in peripheral blood (1-10%). They constitute a unique subset of T lymphocytes that recognize stress ligands or non-peptide antigens through MHC-independent presentation. Major human gd T cell subsets, Vd1 and Vd2, expand in response to microbial infection or malignancy, but possess distinct tissue localization, antigen recognition, and effector responses. We hypothesized that differences at the gene, phenotypic, and functional level would provide evidence that gd T cell subpopulations belong to distinct lineages. Comparisons between each subset and the identification of the molecular determinants that underpin their differences has been hampered by experimental challenges in obtaining sufficient numbers of purified cells. By utilizing a stringent FACS-based isolation method, we compared highly purified human Vd1 and Vd2 cells in terms of phenotype, gene expression profile, and functional responses. We found distinct genetic and phenotypic signatures that define functional differences in gd T cell populations. Differences in TCR components, repertoire, and responses to calcium-dependent pathways suggest that Vd1 and Vd2 T cells are different lineages. These findings will facilitate further investigation into the ligand specificity and unique role of Vd1 and Vd2 cells in early immune responses.

2023-03-29 | GSE224362 | GEO

Distinct gene expression in human Vd1 and Vd2 gd T cells following non-TCR agonist stimulation

2006-02-28 | GSE3720 | GEO

Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the lifespan

Project description:During ontogeny, γδ T cells emerge from the thymus and directly seed peripheral tissues for in situ immunity, though their functional role in humans is largely defined from blood. Here, we analyzed the phenotype, transcriptome, function, and repertoire of human γδ T cells in blood, mucosal and lymphoid tissues from 176 donors across the lifespan, revealing distinct profiles in children compared to adults. In early life, clonally diverse Vd1 subsets predominate across blood and tissues, comprising naïve and differentiated effector and tissue repair functions, while cytolytic Vd2 subsets populate blood, spleen and lungs. Over age, both subsets exhibit clonal expansions disseminated across sites and express elevated cytolytic signatures. In adults, Vd2 cells predominate in blood, while Vd1 cells are enriched across tissues and express residency profiles. These results indicate that antigenic exposures over childhood drive the functional evolution and tissue compartmentalization of γδ T cells, leading to age-dependent roles in immunity.

2024-05-31 | GSE263248 | GEO

RNA sequencing of gamma-delta T cell subsets from young and old mice

Project description:Organismal ageing is associated with loss of immune function and higher incidence of cancer. Whether the γδ T cell pool changes upon organismal ageing is not known. In this study we have characterized γδ T cells in peripheral lymph nodes from old and young mice. We found that the γδ T cell pool is severely altered in old mice. The IL-17 producing γδ lineage becomes dominating while IFN-γ producing γδ1 T cells are declining. γδTCR sequencing revealed no collapse in diversity but oligoclonal expansions in Vγ4 γδ17 subsets. Pro-tumourigenic invariant Vγ6 cells are present only in aged lymph nodes, represent the majority of γδ T cells in the tumour, and are associated with faster tumour progression.

2019-05-22 | E-MTAB-7178 | biostudies-arrayexpress

Intrahepatic CD69+ Vd1 T cells recirculate in the blood of patients affected by liver metastatic colorectal cancer and predict their overall survival

Project description:More than 50% of all patients with colorectal cancer (CRC) develop liver metastasis (CLM) that are characterized by poor prognosis and lack of reliable prognostic markers. Vd1 T cells are gd T innate-like lymphocytes endowed with a broad array of antitumor functions at peripheral tissues, but little is known about their impact in the pathophysiology of CLM. We assessed the phenotype and functions by flow cytometry, clonotype by gdTCR-sequencing, transcriptional profiles by single cell RNA-sequencing and clinical impact of human Vd1 T cells isolated from peripheral blood (PB), tumor-free liver parenchyma surrounding CLM (TFLP) and metastatic tumor (MT) from a large cohort of CLM patients. We show here that CLM tissue is highly enriched of CD69+ Vd1 T effector (TEF) cells in the TFLP area. These cells have a peculiar phenotype, high anti-tumour potential and correlate with a better clinical outcome in terms of lower numbers of liver metastatic lesions and longer overall survival (OS). Moreover, the specific terminally differentiated (TEMRA) CD69+ Vd1 cells can egress CLM tissue to re-circulate in the bloodstream, where they retains high effector functions and show phenotypic/transcriptional and gdTCR profiles that resemble their liver origin. Importantly, high frequencies of CD69+TEMRA Vd1 cells in PB predict a longer OS of CLM patients that is not affected by the neo-adjuvant chemotherapy/immunotherapy regimens administered to CLM patients. The presence at high frequencies of liver memory CD69+TEMRA Vd1 cells in CLM homing to PB represents a new important target to better predict CLM clinical outcomes and to develop novel protocols of adoptive cell transfer therapies.

2023-10-03 | GSE159051 | GEO

Homo sapiens

Project description:Distinct gene expression in human Vd1 and Vd2 gd T cells following non-TCR agonist stimulation

| PRJNA93873 | ENA

Distinct metabolic programs control the effector fate of γδ T cell subsets and their activities in the tumour microenvironment

Project description:Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here we found that γδ T cell subsets making either IFN-γ or IL-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during γδ thymic development, and were stably maintained in the periphery and within tumours.

2020-09-28 | GSE150585 | GEO

TCR-Vγδ usage distinguishes pro- and anti-tumor intestinal γδ T cell subsets

Project description:γδ T cells represent a substantial fraction of intestinal lymphocytes at homeostasis, but also constitute a major lymphocyte population infiltrating colorectal cancers (CRC), albeit their role in CRC remains unclear. Using human CRC samples and murine CRC models, we found that most γδ T cells in pre- or non-tumor colon exhibit cytotoxic markers while tumor-infiltrating γδ T cells express a pro-tumorigenic profile. These contrasting T cell profiles were associated with distinct TCR-Vγδ gene-usage in both mice and humans. Complementary intersectional genetics and antibody-dependent strategies targeting murine γδ T cells enriched in the epithelium at steady state led to heightened tumor development, while targeting γδ subsets that accumulate during CRC resulted in reduced tumor growth. Our results uncover pro- and anti-tumor roles for γδ T cell subsets.

2022-06-14 | GSE205720 | GEO

Single cell RNAseq of human TCRVdelta 1 and TCRVdelta 2 gammadelta T lymphocytes purified from healthy adults blood

Project description:γδ T lymphocytes represent ~1% of human PBMC and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current scRNA-Seq studies do not identify γδ T lymphocytes since their transcriptomes at the single cell level are unknown. Here we show that high resolution clustering of large scRNA-Seq data sets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their TCRVδ1 and TCRVδ2 subsets in large data sets from complex cell mixtures. In t-SNE plots from blood and tumor samples, the few γδ T lymphocytes appear collectively embedded between cytotoxic CD8 T and NK cells. Their TCRVδ1 and TCRVδ2 subsets form close yet distinct sub-clusters respectively neighbouring NK and CD8 T cells owing to expression of shared and distinct cytotoxic maturation genes. Similar pseudo-time maturation trajectories of TCRVδ1 and TCRVδ2 γδ T lymphocytes were discovered, unveiling in both subsets an unattended pool of TEMRA cells with preserved proliferative capacity, a finding confirmed by in vitro proliferation assays. Overall, the single cell transcriptomes of thousands of individual gd T lymphocytes from different CMV+ and CMV- donors reflect cytotoxic maturation stages driven by the immunological history of donors. This landmark study establishes the rationale for identification, subtyping and deep characterization of human γδ T lymphocytes in further scRNA-Seq studies of complex tissues in physiological and disease conditions.

2019-05-01 | GSE128223 | GEO

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