7421 results for "canc*"

in 12.18 milliseconds.

• Vaccine-Expanded Plasmablast-like B Cells Are Associated with Response to Dendritic Cell Therapy in Metastatic Melanoma

  Dendritic cells (DCs), either monocyte-derived (moDCs) or naturally circulating, have been employed in cancer treatment across both metastatic and adjuvant settings. DC vaccines (DC Vax) are capable of inducing tumor-specific immune responses, yet clinical outcomes have thus far fallen short of expectations. Here, we performed a multi-omics analysis of the apheresis product, including CD14⁺ monocytes, and the final DCVax formulation. Among all the components analyzed, the most striking finding was the unexpected presence of CD19⁺ B cells within the DC Vax formulation, which distinguished Responders from Non-Responders to moDC vaccination in metastatic melanoma. The abundance of B cells in DC Vax correlated with their peripheral frequency; however, within the vaccine, these cells acquired a CD20lowCD27hiCD38hi plasmablast-like phenotype, distinct from their autologous circulating B-cell precursors. Notably, a parallel observation was made in Responders, whose pre-treatment lesions were enriched in B cells organized as Tertiary Lymphoid Structures. These results underscore the importance of B cells in both baseline immunity and DCVax formulation, hinting at unexplored mechanisms by which they may influence vaccine effectiveness.

  Study EGAS50000001177

• METABRIC

  The elucidation of breast cancer subgroups and their molecular drivers requires integrated views of the genome and transcriptome from representative numbers of patients. We present an integrated analysis of copy number and gene expression in a discovery and validation set of 997 and 995 primary breast tumours, respectively, with long-term clinical follow-up. Inherited variants (CNVs, SNPs) and acquired somatic copy number aberrations (CNAs) were associated with expression in 40% of genes, although the landscape was dominated by cis and trans-acting CNAs. By delineating expression outlier genes driven in cis by CNAs, we identified putative cancer genes, including deletions in PPP2R2A, MTAP, and MAP2K4. Unsupervised analysis of paired DNA/RNA profiles revealed novel subgroups with distinct clinical outcomes, which reproduced in the validation cohort. These include a high-risk, ER-positive 11q13/14 cis-acting subgroup and a favourable prognosis subgroup devoid of CNAs. Trans-acting aberration 0152hotspots were found to modulate subgroup-specific gene networks, including a TCR deletion-mediated adaptive immune response in the 0152CNA-devoid sub-group and a Basal-specific chromosome 5 deletion-driven mitotic network. Our results provide a novel molecular stratification of the breast cancer population, derived from the impact of somatic copy number aberrations on the transcriptome.

  Study EGAS00000000083

• Spatial transcriptomics of human meningioma samples.

  We performed spatial transcriptomic profiling of human meningioma samples to map gene expression patterns within their native tissue architecture.

  Study EGAS50000001556

• Integrating transcriptional regulatory networks with chromatin accessibility as markers of survival outcome and drug response in triple-negative breast cancer

  Patients with triple-negative breast cancer (TNBC), a highly aggressive and heterogeneous breast cancer subtype, have limited effective targeted therapy options and frequently develop resistance to chemotherapy. Transcription regulators (TRs) guided precision medicine, namely anti-estrogen receptor therapy, has proven successful in hormone-dependent breast cancer, but remains a challenge in TNBC. Here, we identified key TRs underlying TNBC identity by combining a transcriptional interaction network with chromatin accessibility and defined TR activity score metrics. We show that the activity scores of these TRs independently discriminate patient outcome across different clinical endpoints. Matching TR activity scores to drug sensitivity identified drug-TR pairs across independent datasets, including NFE2L3 and CBFB activity associated with sensitivity to mTOR inhibition, which we validated using a cohort of TNBC patient-derived xenografts. Collectively, we present methodology to promote TR-guided precision medicine that captures inter-tumor heterogeneity in TNBC and nominates drug sensitivities according to TR activity scores inferred from expression and chromatin accessibility data.

  Study EGAS50000001691

• ATAC-seq of 38 TNBC Patient Derived Xenograft Models

  Chromatin accessibility profiles from 38 triple‑negative breast cancer (TNBC) patient‑derived xenograft (PDX) tumor samples generated by ATAC‑seq. Fastq files and aligned bam files are uploaded.

  Dataset EGAD50000002430

• Long-read single-cell genome, transcriptome and open chromatin profiling links genotype to phenotypes

  Current single-cell multiomics methods typically provide limited genomic information, constraining genotype-phenotype studies. To address this gap, we developed SPLONGGET (Single-cell Profiling of LONG-read Genome, Epigenome, and Transcriptome), which integrates 10X Genomics barcoding with Oxford Nanopore sequencing to simultaneously profile genome, chromatin accessibility, and full-length transcriptomes in thousands of single cells. By retaining all tagmentation fragments during library preparation, SPLONGGET delivers whole-genome coverage, supports target enrichment for effective single-cell genotyping, and remains backwards compatible with existing short-read workflows. We apply SPLONGGET to longitudinal samples from a case of pediatric B-cell acute lymphoblastic leukemia (B-ALL) to reveal clonal dynamics during therapy and the phenotypic effects of somatic variation, providing valuable insights into disease progression and relapse. In conclusion, SPLONGGET enables integrated high-throughput analysis of genetic variation and molecular phenotypes using off-the-shelf kits, offering a timely and powerful tool to study genetically heterogeneous samples, such as tumours but also ageing normal tissues.

  Study EGAS50000001278

• cell-free Methylated DNA by Immunoprecipitation and Sequencing (cfMeDIP) of human meningioma samples.

  Raw data for cell-free Methylated DNA by Immunoprecipitation and Sequencing (cfMeDIP) of human meningioma samples.

  Study EGAS50000001539

• Proteomics of human cancer-associated T cells identifies regulators of T cell functionality

  CD8⁺ T cells in solid tumors progressively lose anti-tumor activity, yet the cell-intrinsic mechanisms driving this loss of function remain incompletely defined. Here, we performed matched proteomic and transcriptomic profiling of dysfunctional and bystander CD8⁺ tumor-infiltrating T cells isolated from primary tumors of treatment-naïve non-small cell lung cancer patients. Proteomic analysis revealed widespread discordance with mRNA expression, with 8% of differentially expressed proteins detected exclusively at the protein level. Genetic perturbation of such differentially expressed proteins identified the chromatin remodeler CHD4 and fatty acid synthase (FASN) as cell-intrinsic regulators of T cell function. CHD4 deletion promoted effector differentiation and enhanced cytokine production, whereas FASN deletion preserved mitochondrial fitness and sustained T cell functionality under chronic T cell receptor stimulation. Together, these findings demonstrate that proteomic profiling uncovers regulators of T cell functionality that are not apparent from transcriptomic analyses alone, highlighting an additional layer of regulatory control.

  Study EGAS50000001886

• scRNAseq of tumor infiltrating CD8+ T cells

  single cell mRNA sequencing of tumor infiltrating CD8+ T cells. CD8+ T cells were FACS sorted from tumor tissue obtained from 8 non-small cell lung cancer patients. Gene expression and TCR library preparation was performed using the Chromium Next GEM Single Cell 5' Kit v2, Chromium 5' Feature Barcode Kit, and Chromium Single Cell Human TCR Amplification Kit from 10x genomics. After paired-end sequencing this resulted in fastq files containing TCR sequences, gene expression, and feature barcode levels.

  Dataset EGAD50000002739

• Bulk RNAseq of cancer-associated CD8 T cell populations

  Bulk mRNA sequencing of cancer-associated CD8 T cell populations isolated from tumor and tumor-adjacent tissue from non-small cell lung cancer patients. CD8 T cell populations isolated were CD103+CD39- and CD103+CD39+ from tumor tissue, and CD103+CD39- from adjacent tissue. These populations were isolated from 5 patients, totaling 15 samples. bulk poly-A RNA was isolated and libraries were prepped using the Smart-Seq2 protocol, followed by paired-end sequencing (Illumina). Raw data are in fastq format.

  Dataset EGAD50000002740