7359 results for "canc*"

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• Comparison of fresh and slow-frozen cancer samples for different applications

  Surplus tissues from multiple solid human cancers directly slow-frozen after resection can subsequently be used for different types of methods including the establishment of 2D, 3D, and ex vivo cultures as well as single cell RNA sequencing (scRNAseq) with similar results when compared to freshly analyzed material.

  Study EGAS00001005891

• Genetic analysis of HLA and immune escape genes in Diffuse Large B-cell Lymphoma

  Fifty percent of diffuse large B-cell lymphoma (DLBCL) cases lack cell-surface expression of the class-I major histocompatibility complex (MHC-I), thereby escaping immune recognition by cytotoxic T cells. In order to comprehensively identify the mechanisms involved in MHC-I loss, we first performed immunophenotypic analysis of both MHC class-I and -II in 657 cases across the spectrum of B-NHL, revealing that loss of MHC-I, but not MHC-II, is preferentially restricted to DLBCL. We then used whole exome and targeted deep-sequencing to examine genes involved in MHC-I expression in 74 DLBCL samples representative of MHC-I positive and negative cases. We show here that somatic biallelic or monoallelic inactivation of B2M and/or HLA-I is present in 80.9% (34/42) of MHC-I negative tumors. Furthermore, 68.8% (22/32) of MHC-I positive DLBCLs also harbored monoallelic HLA-I genetic alterations (MHC-I positivemono) that lead to allelic imbalance, suggesting allele-specific inactivation. Both MHC-I negative and MHC-I positivemono cases showed a significantly higher mutational burden as well as a higher number of inferred neo-antigens, suggesting co-selection of HLA-I loss and sustained neo-antigen production. Interestingly, the analysis of > 500.000 individuals in two databases revealed homozygosity of germline HLA-I genes in 26-38% of DLBCL patients, a frequency significantly higher than that observed in any other cancer type. In mice, germinal-center B cells lacking HLA-I expression did not progress to lymphoma and were counterselected in the context of oncogene-driven lymphomagenesis, suggesting that additional events are needed to license immune evasion. These results suggest a multi-step process of HLA-I loss including both germ-line and somatic events in DLBCL development, and have direct implications for the pathogenesis and immunotherapeutic targeting of this disease.

  Study EGAS00001005054

• Genetic makeup of agnospheres

  Agnospheres are cultures of cancer stem cells isolated from tissue biopsies from patients with Cancer of Unknown Primary (CUPs). The latter is a lethal malignancy (median survival <1 year), representing approximately the 3% of all cancers, and characterized by metastatic dissemination in the absence of a primary tumor recognizable by a standardized protocol including thorough body imaging and histopathological analysis. Agnospheres are long-term propagated in culture and, after subcutaneous injection into immunocompromised mice, they display high tumorigenicity and quickly reproduce the clinical presentation of the original tumor, featuring a multi-organ metastatic pattern and poorly differentiated histology. The goal of the project is to analyse the mutational profile of agnospheres in detail, as to verify its correspondance with that of the original tumors. Genetic information will be exploited to investigate the genetic drivers of the CUP phenotype, in particular the hypermetastatic ability and the differentiative block.

  Study EGAS00001004868

• Single-cell RNA-seq data from metastatic ovarian cancer for quality control study

  Quality control is a crucial preliminary step in any single-cell RNAseq experiment, where hard thresholds are commonly used. In order to develop a methodology for a more precise cell filtering in the early steps of a scRNAseq data analysis, we collected tissue samples before chemotherapy from 4 patients.

  Study EGAS00001005066

• Cell-free DNA TAPS for early cancer detection

  Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection. However, due to technological challenges associated with DNA methylation sequencing in low input cfDNA samples, most studies have been limited by DNA damage caused by bisulfite sequencing, or the qualitative nature of enrichment-based sequencing. Recently, we developed TET-assisted Pyridine Borane Sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and non-cancer controls. From just 10 ng cfDNA (1-3 mL of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.

  Study EGAS00001004962

• The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival

  Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes (TIL/Tc) could determine disease course at different stages in cancer progression. We show that the diversity of the TIL/Tc TCR at baseline is prognostic in various cancers, whereas in metastatic melanoma TIL/Tc TCR clonality at baseline is predictive for activity and efficacy of PD1 blockade immunotherapy.

  Study EGAS00001005201

• High-grade serous ovarian cancer refined with single-cell RNA-sequencing

  We performed single-cell RNA-sequencing of 18,403 cells unbiasedly collected from 7 treatment-naive HGSOC tumours. For each phenotypic cluster of tumour or stromal cells, we identified specific transcriptomic markers. Next, we explored which phenotypic clusters correlate with overall survival based on expression of these transcriptomic markers in 1467 bulk RNA-seq tumours. By evaluating molecular subtype signatures in single cells, we assessed to what extent a phenotypic cluster of tumour or stromal cells contributes to each molecular subtype.

  Study EGAS00001004987

• INSIGHT: VHL Case Report

  The overall goal of this study is to uncover contributors to inherited cancer through analysis of individuals and families with, or at risk of, a hereditary cancer syndrome. In addition, we hope to elucidate novel mechanisms of tumourigenesis in hereditary cancer patients. This specific report highlights a rare case of VHL mosaicism and shows the value of tissue testing in VHL variant negative cases.

  Study EGAS00001005895

• Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer

  Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit. Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we found a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals. We then derived gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA-seq data. Importantly, we found increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B cells were also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to PD-L1 blockade efficacy in NSCLC.

  Study EGAS00001005013

• Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity and Tumor-Immune Evolution in Refractory Mantle Cell Lymphoma

  The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

  Study EGAS00001005019