Expression data from human brain tumors and human normal brain
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE50161 | GEO | 2013/08/25
SECONDARY ACCESSION(S): PRJNA216955
REPOSITORIES: GEO
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Project description:The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors. Gene expression profiles were used to identify immune marker gene that are differentially expressed between various brain tumor types. Gene expression profiles were generated from surgical tumor and normal brain samples (n=130) using Affymetrix HG-U133plus2 chips (Platform GPL570). Gene expression profiles of different types of brain tumors and normal brain were filtered to obtain gene expression of key immune cell markers. Comparative analyses between different brain tumors and normal brain was used to identifiy differential immune characteristics of these tumors.
2013-08-25 | E-GEOD-50161 | biostudies-arrayexpress
Project description:With the increasing use of immunotherapy in cancer, understanding the tumor immune microenvironment (TIME) has become increasingly important. There has been great success in treatment of some pediatric high-grade gliomas with immune checkpoint inhibition, however overall, the immune microenvironment in pediatric brain tumors remains poorly understood. Accordingly, we developed a clinical immune-oncology gene expression assay and used it to profile a diverse range of pediatric brain tumors with detailed clinical and molecular annotation, including a total of 1379 cases. Our findings demonstrate the critical importance of understanding the TIME to guide the prognosis and management of pediatric brain tumors. In pediatric low-grade gliomas we identified distinct patterns of immune activation with prognostic significance in BRAF V600E mutant tumors. In pediatric high-grade gliomas, we observed elevated inflammation and T cell infiltrates in tumors that have historically been considered immune cold, as well as genomic correlates of inflammation levels. In our cohort of mismatch repair deficient high-grade gliomas treated with immune checkpoint inhibition, we found that high tumor inflammation signature was a significant predictor of treatment response. Furthermore, we demonstrated the potential for multimodal biomarkers to improve the treatment stratification of these patients. Importantly, while overall patterns of immune activation were observed for histologically and genomically defined tumor types, there was nonetheless significant variability within each diagnostic entity, indicating that the immune response must be evaluated as an independent feature. In sum, in addition to the histology and molecular profile, this work establishes the importance of assessing and reporting on the tumor immune microenvironment as an essential axis of cancer diagnosis in the era of personalized medicine.
2024-02-19 | GSE227756 | GEO
Project description:The anatomic location and immunologic characteristics of brain tumors result in strong lymphocyte suppression. Consequently, conventional immunotherapies targeting CD8 T-cells are ineffective against brain tumors. Tumor cells escape immunosurveillance by various mechanisms, and tumor cell metabolism can affect the metabolic states and functions of tumor-infiltrating lymphocytes. Oxygen tension is one important factor influencing immune responses. Here, we discovered that brain tumor cells had a particularly high demand for oxygen, which affected γδ T-cell-mediated antitumor immune responses but not those of conventional T-cells. Specifically, tumor hypoxia activated the γδ T-cell protein kinase A (PKA) pathway at a transcriptional level, resulting in repression of NKG2D expression. Alleviating tumor hypoxia reinvigorated NKG2D expression and the antitumor function of γδ T-cells. These results reveal a hypoxia-mediated mechanism by which brain tumors and γδ T-cells interact and emphasize the importance of γδ T-cells for antitumor immunity against brain tumors.
2020-12-04 | GSE159542 | GEO
Project description:T cell responses within pediatric brain tumors (PBT) remain poorly understood. We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived brain tumor-infiltrating T cells to map T cell molecular profile with TCR repertoire and clonality. We demonstrate marked clonal expansion of intra-tumoral T cells and reveal their differential phenotype, transcriptional state and functional properties within brain tumors. To understand T cell responses within highly immunogenic tumors that respond to checkpoint blockers, we undertook analysis of human non-small cell lung cancer (NSCLC). We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived lung tumor-infiltrating T cells to map T cell molecular profile with clonality.
2024-01-16 | GSE221776 | GEO
Project description:Leukocyte infiltration accelerates brain injury following intracerebral hemorrhage (ICH). But the involvement of T lymphocytes in this process has not been fully elucidated.To further depict the landscape of the composition and functional states of brain-infiltrating immune cells following ICH, single-cell RNA sequencing was performed to compare the molecular characteristics of CD45+ cells from brain and spleen tissues in ICH and control mice.Our results revealed that brain-infiltrating T cells exhibited enhanced pro-inflammatory and pro-apoptotic signatures.
2023-06-07 | GSE230414 | GEO
Project description:Neoantigen discovery in pediatric brain tumors is hampered by their low mutational burden and scant tissue availability. We developed a low-input proteogenomic approach combining tumor DNA/RNA sequencing and mass spectrometry proteomics to identify tumor-restricted (neoantigen) peptides arising from multiple genomic aberrations to generate a highly target-specific, autologous, personalized T cell immunotherapy. Our data indicate that novel splice junctions are the primary source of neoantigens in medulloblastoma, a common pediatric brain tumor. Proteogenomically identified tumor-specific peptides are immunogenic and generate MHC II-based T cell responses. Moreover, polyclonal and polyfunctional T cells specific for tumor-specific peptides effectively eliminated tumor cells in vitro. Targeting novel tumor-specific antigens obviates the issue of central immune tolerance while potentially providing a safety margin favoring combination with other immune-activating therapies. These findings demonstrate the proteogenomic discovery of immunogenic tumor-specific peptides and lay the groundwork for personalized targeted T cell therapies for children with brain tumors.
2021-11-02 | PXD029082 | Pride
Project description:Background<br>Primitive brain tumors are the first cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. <br>Methodology/Principal findings<br>Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). The vast majority (10/12) of high-grade glioma-derived oncospheres sustained long-term self-renewal numbers akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumor types. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P=0.05, chi-square test). TSCs shared a complex molecular profile combining embryonic stem cell markers with elements controlling neural stem cell properties and epithelio-mesenchymal transitions. They were radio- and chemoresistant and formed aggressive tumors after intracerebral grafting. Survival analysis of the cohort showed an association between isolation of TSCs with long-term self-renewal abilities and a patientM-^Rs higher mortality rate (P = 0.022, log-rank test). Patients bearing cells with limited self-renewal properties constituted an intermediate group of survival but which did not reach statistical significance. <br>Conclusions/Significance<br>In brain tumors affecting adult patients, TSC have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.<br>
2011-09-07 | E-MEXP-2910 | biostudies-arrayexpress
Project description:Background<br>Primitive brain tumors are the first cause of cancer-related death in children. Tumor cells with stem-like properties (TSCs), thought to account for tumorigenesis and therapeutic resistance, have been isolated from high-grade gliomas in adults. Whether TSCs are a common component of pediatric brain tumors and are of clinical relevance remains to be determined. <br>Methodology/Principal findings<br>Tumor cells with self-renewal properties were isolated with cell biology techniques from a majority of 55 pediatric brain tumors samples, regardless of their histopathologies and grades of malignancy (57% of embryonal tumors, 57% of low-grade gliomas and neuro-glial tumors, 70% of ependymomas, 91% of high-grade gliomas). The vast majority (10/12) of high-grade glioma-derived oncospheres sustained long-term self-renewal numbers akin to neural stem cells (>7 self-renewals), whereas cells with limited renewing abilities akin to neural progenitors dominated in all other tumor types. Regardless of tumor entities, the young age group was associated with self-renewal properties akin to neural stem cells (P=0.05, chi-square test). TSCs shared a complex molecular profile combining embryonic stem cell markers with elements controlling neural stem cell properties and epithelio-mesenchymal transitions. They were radio- and chemoresistant and formed aggressive tumors after intracerebral grafting. Survival analysis of the cohort showed an association between isolation of TSCs with long-term self-renewal abilities and a patients higher mortality rate (P = 0.022, log-rank test). Patients bearing cells with limited self-renewal properties constituted an intermediate group of survival but which did not reach statistical significance. <br>Conclusions/Significance<br>In brain tumors affecting adult patients, TSC have been isolated only from high-grade gliomas. In contrast, our data show that tumor cells with stem cell-like or progenitor-like properties can be isolated from a wide range of histological sub-types and grades of pediatric brain tumors. They suggest that cellular mechanisms fueling tumor development differ between adult and pediatric brain tumors.<br>
2011-09-07 | E-MEXP-2909 | biostudies-arrayexpress
Project description:This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back (recurrent), progressed, or have not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body’s immune system, and may interfere with the ability of tumor cells to grow and spread.
| 2183538 | ecrin-mdr-crc
Project description:Molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have introduced novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532-NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA-sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532-NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF-NUTM1 fusions and other NUTM1-fusion positive brain tumors reported in literature. Although rare, the distinct pathology and underlying molecular characteristics of these tumors separate them from other embryonal tumors. Therefore, the NUTM-rearrangement appears to define a novel subgroup of pediatric central nervous system embryonal tumors with rhabdoid/epithelioid features that may have a unique response to treatment. Screening for a NUTM1-rearrangement should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis so this can ultimately inform therapeutic management for these patients.
2023-02-28 | GSE226220 | GEO