Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Peripheral clonal expansion of T lymphocytes associates with tumour infiltration and response to cancer immunotherapy

ABSTRACT: We performed single-cell RNA sequencing (scRNA-seq) and deep analysis of T cell receptor (TCR) clonotypes (scTCR-seq) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumours, normal adjacent tissue (NAT), and peripheral blood. In a subset of patients, we find clear evidence of clonotypic expansion of T effector-like cells not only within the tumour but also in NAT.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139555 | GEO | 2019/12/09

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Peripheral clonal expansion of T cells (scRNA-seq)

Project description:We performed single-cell RNA sequencing (scRNA-seq) and deep analysis of T cell receptor (TCR) clonotypes (scTCR-seq) in cancer patients across several indications, assessing the profiles of TCRs in the various populations of T cells in tumours, normal adjacent tissue (NAT), and peripheral blood. In a subset of patients, we find clear evidence of clonotypic expansion of T effector-like cells not only within the tumour but also in NAT.

| EGAS00001003993 | EGA

Peripheral clonal expansion of T cells (scTCR-seq)

| EGAS00001003994 | EGA

scRNA and TCRalpha-beta-seq data from 3 dissociated renal cell carcinoma samples that were CD45 positive sorted, enriched for lymphocytes and sequenced

Project description:In our study, we have characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naive renal cell carcinoma (RCC) patients (n=3), as well as the minimally cultured pre-REP TILs and rapidly expanded REP TILs with a clinical-grade TIL expansion protocol. We observed that the REP TILs encompassed an abundance of CD4positive T-cells, together with increased LAG-3 and low PD-1 expression in the CD4positive and CD8positive T-cells. In addition, we observed that the TIL expansion protocol expanded small CD4positive T-cell clonotypes in the tumor microenvironment (TME), and that the large, exhausted tumor T-cell clonotypes do not expand. We further identified RCC-associated TCR motifs that were validated in multiple TCRalpha-beta-seq and scRNAand TCRalpha-beta-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, immunophenotype, and specificity of the TCRs in RCC TILs.

2023-12-29 | E-MTAB-12910 | biostudies-arrayexpress

Transcriptome-based identification of tumor-reactive and bystander CD8+ T cell receptor clonotypes in human pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is generally refractory to immune checkpoint blockade, although patients with genetically unstable tumors can show modest therapeutic benefit. We previously demonstrated the presence of tumor-reactive CD8+ T cells in PDAC samples. Here, we charted the tumor-infiltrating T cell repertoire in PDAC by combining single-cell transcriptomics with functional testing of T cell receptors (TCRs) for reactivity against autologous tumor cells. On the basis of a comprehensive dataset including 93 tumor-reactive and 65 bystander TCR clonotypes, we delineated a gene signature that effectively distinguishes between these T cell subsets in PDAC, as well as in other tumor indications. This revealed a high frequency of tumor-reactive TCR clonotypes in three genetically unstable samples. In contrast, the T cell repertoire in six genetically stable PDAC tumors was largely dominated by bystander T cells. Nevertheless, multiple tumor-reactive TCRs were successfully identified in each of these samples, thereby providing a perspective for personalized immunotherapy in this treatment-resistant indication.

2024-01-26 | GSE254250 | GEO

PD-1 Expression Status on CD8+ Tumour Infiltrating Lymphocytes Associates With Survival in Cervical Cancer.

Project description:Despite the expansion of PD-1 checkpoint blockade to multiple types of cancer, whether the programmed cell death 1 (PD-1) expression status on CD8+ tumour infiltrating lymphocytes (TILs) could be a prognostic factor in cervical cancer is still unclear. In this study, we performed ex vivo phenotypic analysis of PD-1 expression on CD8+ TILs by flow cytometry from 47 treatment-naïve cervical cancer patients. With a median follow-up of 26.1 months (95% confidence interval [CI], 24-28.2 months), we then linked the quantitative cellular expression results to progression-free survival and overall survival. Based on the intensity of PD-1 expression, we further categorised the cervical cancer patients into PD-1high expressers (29.8%, 14/47) and PD-1low expressers (70.2%, 33/47). Multivariate analysis revealed that PD-1high expressers are correlated with early recurrence (HR, 5.91; 95% CI, 1.03-33.82; P= 0.046). Univariate analysis also demonstrated that PD-1high expressers are associated with poor overall survival in cervical cancer (HR, 5.365; 95% CI, 1.55-18.6; P=0.008). Moreover, our study also demonstrated that CD8+/CD4+ TIL ratio and HPV infection status are risk factors for early relapse and mortality in cervical cancer patients. In conclusion, this study confirms that PD-1 expression status is an independent prognostic factor for progression free survival in cervical cancer. These findings could be important in predicting the relapse of cervical cancer as a cellular diagnosis method and could be important knowledge for the selection of prospective PD-1 blockade candidates.

| S-EPMC8212040 | biostudies-literature

Peripheral clonal expansion of T lymphocytes associates with tumour infiltration and response to cancer immunotherapy

Project description:Peripheral clonal expansion of T lymphocytes associates with tumour infiltration and response to cancer immunotherapy

| PRJNA580251 | ENA

scRNA/TCR-seq of CD8+CD44+ T cells from tumor draining lymph node and matched vitiligo-affected skin of MAV mice

Project description:Purpose: To identify the presence of endogenous tumor-specific TRM cells in LNs, scRNAseq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics in DLNs. Methods: CD8+CD44+ T cells were sorted from DLN and skin of MAV mice and scRNA-seq in parallel with scTCR-seq was performed. Results: The twenty most expanded clonotypes identified in vitiligo-affected skin of these mice, eight matched to lymph nodes and strikingly, those lymph node clonotypes that had matches in skin mapped almost exclusively to the LN TRM cluster Conclusions: Endogenous tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

2021-07-04 | GSE169238 | GEO

ATLAS-seq: a novel microfluidic single-cell TCR screen for highly reactive antigen-specific TCRs

Project description:Clonotype selection of T cell receptors (TCRs) have been the core component of TCR therapy development. However, the conventional and widely used major histocompatibility complex (MHC) multimer staining technologies focus on high-affinity interactions between TCR and MHC-antigen complex, which may fail to identify TCRs with high efficacy for activating T cells. Here, we developed the Aptamer-based T Lymphocyte Activity Screening and sequencing (ATLAS-seq) method on a microfluidic platform. ATLAS-seq isolates and characterizes activated T cells using an aptamer-based fluorescent molecular sensor to monitor cytokine secretion from single-T cells upon antigen stimulation, followed by single-cell sequencing. As a proof of principle study, we used ATLAS-seq to screen cytomegalovirus (CMV)-reactive TCRs and identified a distinct clonotype population with a higher T cell activation level compared to one recovered by Dextramer staining method. Furthermore, we observed that ATLAS-seq selected TCR clonotypes are more efficient in target cell killing than those from Dextramer staining. Therefore, our ATLAS-seq can provide an efficient workflow to screen highly reactive antigen-specific TCR clonotypes for cancer immunotherapy.

2024-10-11 | GSE234359 | GEO

Decreased cytotoxic T cells and TCR clonality in organ transplant recipients with squamous cell carcinoma

Project description:T-cell landscape differences between cutaneous squamous cell carcinoma (cSCC) tumors in immune competent (SCC in IC) and immunocompromised organ transplant recipients (TSCC in OTR) are unclear. We developed an analytical method to define tumor infiltrating lymphocyte (TIL) phenotype in cSCC from immune competent and immune suppressed patients using single-cell TCR sequencing and gene expression data. TSCC exhibits reduced proportions of cytotoxic and naïve TILs and similar numbers of regulatory TILs. Fewer, more heterogeneous TCR clonotypes are observed in TIL from OTR. Most TCR sequences for top ten clonotypes correspond to known antigens, while 24% correspond to putative neoantigens. OTR show increased cSCC events over 12 months possibly due to reduced cytotoxic T-cells. Our novel method of barcoding CD8+ T-cells is the first providing gene expression and TCR sequences in cSCC. Knowledge regarding putative antigens recognized by TCRs with phenotypic function of T-cells bearing those TCRs could facilitate personalized cSCC treatments.

2020-06-03 | GSE145328 | GEO

Single-cell RNA-seq of tumor-infiltrating lymphocytes in metastatic uveal melanoma

Project description:Metastatic uveal melanoma generally responds poorly to immunotherapy. The aim here was to sequence tumor-infiltrating lymphocytes from uveal melanoma metastases to study their phenotypes and T-cell receptor (TCR) clonotypes. We performed paired single-cell transcriptome and TCR sequencing using the 10x Genomics platform of IL2-expanded tumor-infiltrating lymphocytes from 7 liver and 1 subcutaneous metastasis.

2020-03-16 | E-MTAB-8846 | biostudies-arrayexpress

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