Project description:Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy necessitates optimization and maintenance of activated effector T cells (Teffs). We prospectively collected and applied multi-omics analysis to paired, pre- and post-treatment PDAC specimens collected in a platform neoadjuvant study of GVAX vaccine +/- nivolumab (anti-PD-1) to uncover sensitivity and resistance mechanisms. We show that GVAX-induced tertiary lymphoid aggregates become immune-regulatory sites in response to GVAX+nivolumab. Higher densities of tumor-associated neutrophils (TANs) following GVAX+nivolumab portend poorer overall survival (OS). Increased T cells expressing CD137 associated with cytotoxic Teff signatures and correlated with increased OS. Bulk and single-cell RNA-sequencing found that nivolumab alters CD4+ T cell chemotaxis signaling in association with CD11b+ neutrophil degranulation, and CD8+ T cell expression of CD137 required for optimal T cell activation. These findings provide new insights into PD-1-regulated immune pathways in PDAC that should inform more effective therapeutic combinations that include TAN regulators and T cell activators.

2022-03-07 | GSE197613 | GEO

Whole-exome sequencing (WES) of single glands from opposite side of two colorectal tumors and WES of colorectal cancer xenografts derived from single cell culture to study tumor growth dynamics

Project description:Single Gland Whole-exome sequencing: building on our prior description of multi-region WES of colorectal tumors and targeted single gland sequencing (E-MTAB-2247), we performed WES of multiple single glands from different sides (right: A and left: B) of two tumors in this study (tumor O and U) on the illumina platform using the Agilent SureSelect 2.0 or illumina Nextera Rapid Capture Exome kit (SureSelect or NRCE, as indicated in the naming of fastq files). Colorectal Cancer Xenograft Whole-exome sequencing: The HCT116 and LoVo Mismatch-Repair-deficient colorectal adenocarcinoma cell lines were obtained from the ATCC and cultured under standard conditions. For both cell lines, a single âfoundingâ cell was cloned and expanded in vitro to ~6M cells. Two aliquots of ~1M cells were subcutaneously injected into opposite flanks (right and left) of a nude mouse and tumors allowed to reach a size of ~1B cells (1cm3) before the animal was sacrificed. Tumor tissue was collected separately from the right and left lesions and DNA was extracted for WES using the illumina TruSeq Exome kit or Nextera Rapid Capture Exome expanded Kits (Truseq or NRCEe), as was DNA from the first passage population (a polyclonal tissue culture for HCT116 and a polyclonal xenograft sample for LoVo), which were employed as a control to study mutation accumulation in culture and post xenotransplantation.

2017-05-01 | E-MTAB-5547 | biostudies-arrayexpress

Capturing the dynamic interactions between tumor and immune components of the tumor micro-environment is important for determining efficacy of anti-PD1 treatment [Post Culture_Metadata]

Project description:RNA extracted from the post 72 hour cultured tumor samples from 31 patients with head and neck squamous cell carcinoma treated Nivolumab and Nivolumab+Ipilimumab was analyzed on the nCounter system using the Pan cancer IO360 panel.

2024-01-09 | GSE234136 | GEO

Quantitative proteomics identifies plasma protein alterations that associate with metabolic and thrombotic profile changes after bariatric surgery

Project description:This study involved the collection of 25 (16 female and nine male adults) plasma samples from bariatric surgery patients. Plasma was prepared from blood samples taken pre-surgery (within 48 hours, files with the suffix ‘Pre’) and nine months post-surgery (files with the suffix ‘Post’).

2025-03-17 | PXD057848 | Pride

Whole exome sequencing of 12 NSCLC samples from 4 patients at MDACC

Project description:Multi-region WES from 4 NSCLC patients, totaling 12 tumor samples and 4 matched control samples.

| EGAS00001005829 | EGA

Soluble Guanylate Cyclase Signalling Mediates Etoposide Resistance in Progressing Small Cell Lung Cancer

Project description:We exploited six paired pre-treatment and post-chemotherapy circulating tumour cell patient-derived explant (CDX) models from donors with extensive stage SCLC to investigate changes at disease progression after chemotherapy. WES data from the patient germ line and from the biopsy of the solid tumour is reported in this submission and RNASeq data from these models is reported previously (E-MTAB-8465 - RNA of Small Cell Lung Cancer Circulating Tumour Cells Derived Explants). Both chemo naive and progression models were taken from patients and their drug sensitivity tested within the mouse models. Blood samples were taken from patients, and RosetteSep CTC Enrichment was used to implant these cells into mice. Tumours were allowed to grow, then extracted and re-implanted into second and third generations of mice, before finally being subjected to molecular profiling.

2021-09-15 | E-MTAB-10880 | biostudies-arrayexpress

Methylome profiling of human glioblastoma using Illumina 450K microarrays for the GlioTeX panel

Project description:Genome-wide methylation profiles were generated as part of a multi-omics characterization (SNP array, WES, RNA-seq, cDNA microarray) of a panel of gliomasphere cell lines and matched parental tumors. See https://www.ncbi.nlm.nih.gov/pubmed/27571888 about the GlioTeX panel. Methylation profiling data in this record come from tumour samples. SNP array (ArrayExpress E-MTAB-4804), cDNA microarray (ArrayExpress E-MTAB-4803), WES and RNAseq (European Genome-Phenome Archive EGAS00001001871) have been published before. In addition, for the current project we compare 450K methylation data to nanopore sequencing based methylation profiles. These sequencing data will be accessible via European Genome-Phenome Archive (EGAS00001002213). Please also refer to https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-5795/files/E-MTAB05795.additional.1.zip for further information on the background of this multi-omics study.

2017-06-24 | E-MTAB-5797 | biostudies-arrayexpress

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