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ScRNA-Seq of peripheral CD8 T cells from patients with metastatic melanoma taking ICI therapy.

ABSTRACT: scRNA-Seq of peripheral CD8 T cells from patients with metastatic melanoma taking ICI therapy.

PROVIDER: PRJNA699546 | ENA |

REPOSITORIES: ENA

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scRNA-Seq of peripheral CD8 T cells from patients with metastatic melanoma taking ICI therapy.

Project description:Patients with metastatic melanoma have been treated with the new class of drug named immune checkpoint inhibitors. Single-cell RNA-sequencing was performed in circulating CD8+ T cells isolated by cell sorting from 20 patients who were followed for 6 months. Among them, 11 responded to therapy, whilst 9 did not. Overall, the data obtained by sc-RNA seq showed the presence of MAIT cells, that had higher levels in those who showed a better response to treatment.

2021-02-05 | GSE166181 | GEO

Plasma glycoproteomic biomarkers identify metastatic melanoma patients with reduced clinical benefit from immune checkpoint inhibitor therapy

Project description:The clinical success of immune-checkpoint inhibitors (ICI) in both resected and metastatic melanoma has confirmed the validity of therapeutic strategies that boost the immune system to counteract cancer. However, half of patients with metastatic disease treated with even the most aggressive regimen do not derive durable clinical benefit. Thus, there is a critical need for predictive biomarkers that can identify individuals who are unlikely to benefit with high accuracy, so that these patients may be spared the toxicity of treatment without the likely benefit of response. Ideally, such an assay would have a fast turnaround time and minimal invasiveness. Here, we utilize a novel platform that combines mass spectrometry with an artificial intelligence-based data processing engine to interrogate the blood glycoproteome in melanoma patients before receiving ICI therapy. We identify 143 biomarkers that demonstrate a difference in expression between the patients who died within six months of starting ICI treatment and those who remained progression-free for three years. We then develop a glycoproteomic classifier that predicts benefit of immunotherapy (HR=2.7; p=0.026) and achieves a significant separation of patients in an independent cohort (HR=5.6; p=0.027). To understand how circulating glycoproteins may affect efficacy of treatment, we analyze the differences in glycosylation structure and discover a fucosylation signature in patients with shorter overall survival (OS). We then develop a fucosylation-based model that effectively stratifies patients (HR=3.5; p=0.0066). Together, our data demonstrate the utility of plasma glycoproteomics for biomarker discovery and prediction of ICI benefit in patients with metastatic melanoma and suggest that protein fucosylation may be a determinant of anti-tumor immunity.

2023-05-31 | MSV000092069 | MassIVE

Bulk RNA seq profile of CD8+ T cells in peripheral blood lymphocytes from 28 melanoma patients

Project description:CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we profiled transcriptome of CD8+ T cells in peripheral blood lymphocytes of 28 melanoma patients that responded to ICI or not using bulk RNA sequencing.

2021-11-16 | GSE171256 | GEO

RNA seq data of CD8+ T cells in peripheral blood lymphocytes from melanoma and lung cancer patients

Project description:CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we profiled transcriptome of CD8+ T cells in peripheral blood lymphocytes of 4 melanoma and 4 lung cancer patients that responded to ICI or not using RNA sequencing.

2021-11-17 | GSE152590 | GEO

CD8+ T cells in peripheral blood lymphocytes and tumor-infiltrating lymphocytes of melanoma patients: additional validation data

Project description:CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we conduct single cell RNA sequencing of CD8+ T cells in peripheral blood or tumor lymphocytes of 2 additional melanoma patients.

2021-11-16 | GSE153098 | GEO

CD8+ T cells in peripheral blood lymphocytes and tumor-infiltrating lymphocytes of melanoma patients

Project description:CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of melanoma. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. In the hope of remedying this challenge, we conducted single-cell transcriptomic analyses of CD8+ T cells in peripheral blood lymphocytes (CD8-mPBLs) and, importantly, tumor-infiltrating lymphocytes (CD8-mTILs) from 8 patients with metastatic melanoma.

2021-11-16 | GSE138720 | GEO

scRNA-seq and differential expression analyses of metastatic melanoma cells before, during and after tumour escape

Project description:Highly invasive integrin and protease-independent amoeboid migration is often employed by cancer cells at the invasive front, though little is known about the transcriptomic changes underlying the switch to an amoeboid migratory mode. Using a metastatic melanoma cell line expressing photoconvertible Dendra2 protein (WM983c-D2), tumour spheroids were cultured in 3D collagen matrices and imaged over time. Spheroids grown from WM983c-D2 cells generate cells of three distinct phenotypes: 1) compact, non-invading cells organised at the spheroid surface with no visual cell protrusions, hereafter termed ‘epithelial’; 2) cells still attached to the spheroid periphery that have commenced tumour escape, exhibiting cellular protrusions and an elongated phenotype, hereafter termed ‘escaping’; 3) singly migrating cells exhibiting a rounded phenotype and no lamellipodia consistent with amoeboid cell migration, hereafter termed 'amoeboid'. Individual amoeboid and escaping cells, as well as groups of epithelial cells at the spheroid edge were photoconverted and single cell sorted via FACS following enzymatic digestion of the collagen matrix. 10 Epithelial, 12 escaping and 13 amoeboid cells were subjected to scRNA-seq and differential expression analyses in order to identify changes in gene expression as melanoma cells convert from a non-invasive epithelial state to invasive amoeboid cells.

2022-05-21 | E-MTAB-11722 | biostudies-arrayexpress

Promoter methylation data: OHT/ICI-sensitive vs. -resistant cell lines

Project description:MCF7 breast cancer cell lines: drug-resistant (OHT and ICI) cell lines vs. drug-sensitive (wild type) cell lines. Assessment of association between gene expression and methylation. Two comparisons: OHT-resistant vs. wild type, and ICI-resistant vs. wild type. OHT: 4-hydroxytamoxifen ICI: fulvestrant ((ICI 182780) This submission represents the methylation component of the study.

2011-10-04 | E-GEOD-25519 | biostudies-arrayexpress

Transcription profiling of human MCF-7 breast cancer cells treated with E2, ICI 182,789 (ICI), Raloxifene (Ral), and/or trans-hydroxytamoxifen (TOT)

Project description:MCF-7 breast cancer cells were treated with E2, ICI 182,789 (ICI), Raloxifene (Ral), and/or trans-hydroxytamoxifen (TOT) for 8 or 48 h. Duplicate samples are labeled set A or set B.

2007-09-27 | E-GEOD-848 | biostudies-arrayexpress

Estradiol and ICI 182,780 infusions induce similar transcriptomic response in late gestation fetal hypothalamus

Project description:Estradiol plays a critical role stimulating the fetal hypothalamus-pituitary-adrenal axis at the end of gestation. Estradiol action is mediated through nuclear and membrane receptors that can be modulated by ICI 182,780, a pure anti-estrogen compound. The objective of this study was to evaluate the transcriptomics of estradiol and ICI 182,780, testing the hypothesis that ICI 182,780 blocks the action of estradiol in the fetal hypothalamus. However, we found that a short term (48 hrs) infusion with ICI 182,780 induces a similar transcriptomic response than estradiol infusion in the late gestation ovine fetal hypothalamus, being more evident with higher doses of ICI 182,780. These results suggest that ICI 182,780 is primarily an agonist of estradiol in the developing brain.

2018-01-31 | GSE99497 | GEO

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