Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Moon Hee Lee

PROVIDER: E-MTAB-12910 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

The immunological characterization of expanded tumor-infiltrating lymphocytes in renal cell carcinoma patients

Project description:In this study, we comprehensively characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naÃƒÂ¯ve RCC patients, as well as the corresponding Ã¢Â€ÂœyoungÃ¢Â€Â TILs (pre-REP TILs) and Ã¢Â€Âœrapidly expandedÃ¢Â€Â TILs (REP TILs) following a clinical-grade TIL production protocol. From our scRNA+TCRÃŽÂ±ÃŽÂ²-seq and TCRÃŽÂ²-seq analyses, we show that the REP protocol preferentially favors the expansion CD4+ T-cells that originate from small T-cell clones in the tumor microenvironment (TME), indicating that the large, exhausted T-cell clones in the tumor do not expand during the protocol. We further identified RCC-associated TCR motifs that were validated in multiple TCRÃŽÂ±ÃŽÂ²-seq and scRNA+TCRÃŽÂ±ÃŽÂ²-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, phenotype, and specificity of the TCRs in RCC TILs.

| EGAS00001006952 | EGA

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

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scTCR-seq]

Project description:Adoptive cell therapy (ACT) using in vitro expanded tumor-infiltrating lymphocytes (TILs) has inconsistent clinical responses. To better understand determinants of therapeutic success, we tracked TIL clonotypes from baseline tumors to ACT products and post-ACT blood and tumor samples in melanoma patients using single-cell RNA and T cell receptor (TCR) sequencing. Patients with clinical responses had baseline tumors enriched in tumor-reactive TILs, and these were more effectively mobilized upon in vitro expansion, yielding products enriched in tumor-specific CD8+ cells that preferentially infiltrated tumors post-ACT. Conversely, lack of clinical responses was associated with tumors devoid of tumor-reactive resident clonotypes and with cell products mostly composed of blood-borne clonotypes that persisted in blood but not in tumors post-ACT. Upon expansion, tumor-specific TILs lost tumor-associated transcriptional signatures, including exhaustion, and responders exhibited an intermediate exhausted effector state after TIL engraftment in the tumor, suggesting functional reinvigoration. Our findings provide insight into the nature and dynamics of tumor-specific clonotypes associated with clinical response to TIL-ACT, with implications for treatment optimization.

2023-08-01 | GSE229860 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [scRNA-seq]

2023-08-01 | GSE229858 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [multiome]

2024-09-13 | GSE261023 | GEO

Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma [TCR-Seq]

2023-08-01 | GSE234352 | GEO

Human CD28+/- tumor infiltrating lymphocytes gene expression

Project description:This analysis reveals the different gene expression profiles between human melanoma tumor infiltrating lymphocytes subsets CD8+CD28+ and CD8+CD28-. Adoptive cell therapy (ACT) is an effective approach that removes tumor-infiltrating lymphocytes (TILs) from this suppressive tumor microenvironment and expands and activates CD8+ and CD4+ T cells in vitro, differentiating them into potent anti-tumor effector cells that can be re-introduced back into patients. One of the key problems that may limit tumor regression and long-term durable clinical responses in ACT is the persistence of TILs following infusion. Our study has indicated that ex vivo expanded TILs to be hypo-responsive to peptide re-stimulation, manifested in slow entry into cell cycle and increased apoptosis. Phenotypic and functional analysis using a number of different T-cell differentiation markers found that CD28 was markedly down-modulated in post-REP cells, while CD27 and CD57 levels showed no statistically-relevant changes in expression. Here on a global gene expression level, microarray gene chip analysis of sorted CD8+CD28+ and CD8+CD28- post-REP TILs revealed a number of key differences in their gene expression profiles; notably, an increase in KIR family member expression, loss of p53-binding proteins, and lower CD127/IL-7Ra gene expression found in the CD28- population. On top of advancing T cell phenotype, reactivation and memory, this set of data may also provide insight for ACT clinical protocol optimization to improve TIL response in vivo.

2009-06-10 | GSE16517 | GEO

Fluidigm single-cell RNA-seq analysis for gene signatures associated with T-cell persistence

2020-08-28 | GSE136610 | GEO

Single-cell transcriptome analysis reveals gene signatures associated with T-cell persistence following adoptive cell therapy

Project description:A patient (4095) with metastatic colorectal cancer was treated with polyclonal tumor infiltrating lymphocytes (TILs) targeting the KRAS(G12D) hotspot mutation. Three dominant clonotypes specifically recognizing KRAS(G12D) epitopes were identified, but we found that only two clonotypes persisted 40 days after TIL treatment. Because of these findings, in this study, we utilized a 10X system to perform single-cell TCR/transcriptome analysis for the TILs isolated from this patient, together with 4 additional TILs isolated from 4 patients (4007, 4069, 4071, 4081) treated within 5-month window. In addition, we performed single-cell TCR/transcriptome analysis on Patient 4095's peripheral blood lymphocytes (PBL) day 12 or day 40 after TIL treatment. We also utilized a low-throughput Fluidigm C1 system to perform single-cell RNA-Seq on TIL4095. Please use accession number GSE136610 to find the dataset.

2019-09-10 | GSE136394 | GEO

Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression

Project description:In contrast to its inhibitory effects on many cells, IL-10 activates CD8+ tumor infiltrating lymphocytes (TILs) and enhances their antitumor activity. However, how IL-10 globaly regualte TIL CD8+ T cell function is stil not clear. To understand the transcriptional regulation of TIL CD8+ T cell by IL-10, we performed a microarray analysis using in vitro expanded HUMAN LUNG CANCER TIL CD8 T cells with or without IL-10.

2017-03-01 | GSE79127 | 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