Ena-DATASET-MUG-28-07-2021-09:52:18:534-653 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001007930 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Aligned NGS data (BAM) of 77 frequently mutated genes in cancer using the AVENIO Expanded platform.
| EGAD00001010294 | EGA
Project description:An established mechanism contributing to Immune Checkpoint Inhibitor (ICI) therapy failure is tumor evasion of T-cell responses via downregulation of human leukocyte antigen (HLA). Conversely, the effector function of Natural Killer (NK) cells is enhanced in the absence of HLA expression, making NK-based cellular therapies an attractive option for tumors that are resistant to ICIs. We investigated the preclinical efficacy of using selective isolation of NK cells and harvesting of NKEVs in NSCLC. Single-cell RNAseq (scRNAseq) was used to examine the cellular landscape in PBMCs and tumor tissue. NK cells were isolated from PBMCs, expanded in vitro, and NK-derived EVs (NKEV) were collected and the EV RNA and protein cargo was characterized using proteomics and transcriptomics. The functional capabilities of patient derived NKEVs were assayed with 3-dimensional organoid-like structures derived from patient tumor cells. This work described the cellular landscape in NSCLC circulating and tumor infiltrating immune cells. Additionally, it demonstrated that NKEVs can be successfully harvested from patient derived, expanded NK cells, and highlighted their anti-tumor properties in combination with standard-of-care therapies.
2025-07-09 | GSE274595 | GEO
Project description:An established mechanism contributing to Immune Checkpoint Inhibitor (ICI) therapy failure is tumor evasion of T-cell responses via downregulation of human leukocyte antigen (HLA). Conversely, the effector function of Natural Killer (NK) cells is enhanced in the absence of HLA expression, making NK-based cellular therapies an attractive option for tumors that are resistant to ICIs. We investigated the preclinical efficacy of using selective isolation of NK cells and harvesting of NKEVs in NSCLC. Single-cell RNAseq (scRNAseq) was used to examine the cellular landscape in PBMCs and tumor tissue. NK cells were isolated from PBMCs, expanded in vitro, and NK-derived EVs (NKEV) were collected and the EV RNA and protein cargo was characterized using proteomics and transcriptomics. The functional capabilities of patient derived NKEVs were assayed with 3-dimensional organoid-like structures derived from patient tumor cells. This work described the cellular landscape in NSCLC circulating and tumor infiltrating immune cells. Additionally, it demonstrated that NKEVs can be successfully harvested from patient derived, expanded NK cells, and highlighted their anti-tumor properties in combination with standard-of-care therapies.
2025-07-09 | GSE274588 | GEO
Project description:An established mechanism contributing to Immune Checkpoint Inhibitor (ICI) therapy failure is tumor evasion of T-cell responses via downregulation of human leukocyte antigen (HLA). Conversely, the effector function of Natural Killer (NK) cells is enhanced in the absence of HLA expression, making NK-based cellular therapies an attractive option for tumors that are resistant to ICIs. We investigated the preclinical efficacy of using selective isolation of NK cells and harvesting of NKEVs in NSCLC. Single-cell RNAseq (scRNAseq) was used to examine the cellular landscape in PBMCs and tumor tissue. NK cells were isolated from PBMCs, expanded in vitro, and NK-derived EVs (NKEV) were collected and the EV RNA and protein cargo was characterized using proteomics and transcriptomics. The functional capabilities of patient derived NKEVs were assayed with 3-dimensional organoid-like structures derived from patient tumor cells. This work described the cellular landscape in NSCLC circulating and tumor infiltrating immune cells. Additionally, it demonstrated that NKEVs can be successfully harvested from patient derived, expanded NK cells, and highlighted their anti-tumor properties in combination with standard-of-care therapies.
2025-07-09 | GSE274584 | GEO
Project description:The AVENIO ctDNA Expanded Kit is a next-generation sequencing (NGS) liquid biopsy assay with a 77 gene panel (192 kb) containing genes in U.S. National Comprehensive Cancer Network (NCCN) Guidelines and emerging cancer biomarkers. This pan-cancer assay was applied to 48 plasma samples from patients with breast, colorectal and non-small cell lung cancer. After sequencing 150bp paired-end, reads were aligned to the hg38 genome with the AVENIO Oncology Analysis Software (version 2.0). These files are the deduplicated alignments generated by the analysis software used for subsequent variant, indel and CNV calling.
| EGAD00001006301 | EGA
Project description:Immune checkpoint inhibitor (ICI) therapies present a pillar of modern cancer therapy but can cause severe and potentially fatal neurological immune-related adverse events (n-irAEs). Here, we performed single-cell RNA sequencing and T cell receptor profiling of PBMCs of a cohort of 17 cancer patients receiving ICI therapy. Our data suggest alterations in regulatory T cell frequencies and B cell states, and a significant enrichment of clonally expanded CD4+ cytotoxic T lymphocytes (CD4+ CTLs) with an effector gene expression profile in n-irAE patients.
2025-12-03 | GSE278119 | GEO
Project description:Single-Cell RNA Sequencing of Baseline PBMCs Predicts ICI efficacy and irAE Severity in NSCLC Patients
| PRJNA1206711 | ENA
Project description:Treatment of non-small cell lung cancer (NSCLC) has drastically changed in recent years owing to the robust anti-cancer effects of immune-checkpoint inhibitors (ICI). However, only 20% of NSCLC patients benefit from ICIs, highlighting the need to uncover the mechanisms mediating resistance. By analyzing the overall survival (OS) and mutational profiles of 424 NSCLC patients who received ICI treatments between 2015 and 2021, we determined that patients carrying a loss of function mutation in neurotrophic tyrosine kinase receptor 1 (NTRK1) had a prolonged OS compared to patients with wild-type NTRK1. Notably, suppression of the NTRK1 pathway by knockdown or Entrectinib treatment significantly enhanced ICI efficacy in mouse NSCLC models. RNA sequencing of tumors and NTRK1 knockdown cell lines were performed to demonstrates the role for NTRK1 signaling.
2024-08-20 | GSE274960 | GEO
Project description:Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have demonstrated outstanding clinical efficacy in the treatment of NSCLC patients, ICIs-based therapy has also been associated with a paradoxical acceleration of tumor growth defined as hyperprogressive disease (HPD). In this paper we evaluated distinct plasticity traits in a model of HPD-NSCLC, with the aim of clarifying the mechanisms contributing to ICI resistance that involve IFN-γ and PD-L1. For this purpose, primary cell cultures were established from two stage IV NSCLC samples obtained from a single patient: one, prior to ICI initiation (NSCLC-B, baseline) and the other at the time of radiological evidence of hyperprogression under ICI treatment (NSCLC-H, hyperprogression). Compared to NSCLC-B cells, NSCLC-H cells exhibited a more aggressive in vivo and in vitro behavior, higher MAPK activation and owned the ability to develop tumoroids. The 3500 differentially expressed transcripts, according to whole transcriptome analysis, well described the profound plastic evolution of cells from NSCLC-B to NSCLC-H culture, as well as the increase of CD44 in the NSCLC-H cell line model, in which transcripts of CD44 isoforms lacking the variant domain were abundant. Transcripts of genes involved in the cellular response to IFN-γ were down-modulated in NSCLC-H compared to NSCLC-B, together with CD274. Conversely, an up-regulation of genes related to inflammatory response, including IL1- and IFNGR1, was found. In vitro response to IFN- γ was compromised in both NSCLC-B and NSCLC-H cells, since IFN- γ failed to exert its antiproliferative effect on these cells and to effectively induce PD-L1 expression in 2D-growth assays. Nevertheless, the cytokine induced the activation of both type I and type II IFN-pathway mediators. In addition, treatment with IFN-γ induced NSCLC-H traits in NSCLC-B cells, promoting a striking increase in the number of NSCLC-B 3D-soft agar colonies. Low IFN-γ doses or modulation of PD-L1 contributed to the evolution of NSCLC-B towards NSCLC-H phenotype through the augment of CD44 on cell membrane, cell morphological changes and increased cell growth or sphere formation ability. In conclusion, we report a modulation of plasticity by PD-L1 modulation and IFN-γ in a NSCLC cell culture established from a treatment-naïve patient, who developed HPD under ICI therapy, suggesting an association between NSCLC plasticity and these main actors involved in ICI activity.
2024-12-31 | GSE255144 | GEO
Project description:To investigate a non-invasive strategy for immune monitoring the peripheral blood by flow cytometry, to address the critical need to itdentify predictive immunological biomarkers that correlate with treatment response Peripheral blood mononuclear cells (PBMCs) from 19 non–small-cell lung cancer (NSCLC) patients before and after ICI treatment and four healthy human donors were evaluated, utilizing spectral flow to monitor 24 immune cell markers simultaneously over the course of treatment. We performed immune cell profiling analysis using data obtained from RNA-seq of 19 different patients before and after immunotherapy, to validate the multi-color flow based immune profiling
2023-08-03 | GSE235048 | GEO