دورية أكاديمية
Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma.
| العنوان: | Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma. |
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| المؤلفون: | Close, HJ, Stead, LF, Nsengimana, J, Reilly, KA, Droop, A, Wurdak, H, Mathew, RK, Corns, R, Newton-Bishop, J, Melcher, AA, Short, SC, Cook, GP, Wilson, EB |
| المساهمون: | Melcher, Alan |
| بيانات النشر: | OXFORD UNIV PRESS |
| سنة النشر: | 2020 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Killer Cells, Natural, Cells, Cultured, Cell Line, Tumor, Humans, Glioblastoma, Brain Neoplasms, Prognosis, Cohort Studies, Gene Expression Profiling, Signal Transduction, Cytotoxicity, Immunologic, Immune Tolerance, Gene Expression Regulation, Neoplastic, Phenotype, Gene Regulatory Networks, Neoplastic Stem Cells, Tumor Microenvironment |
| الوصف: | Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem-like cells, a source of post-treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM-infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)-β-mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single-cell transcriptomics demonstrated that both tumour and haematopoietic-derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co-expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti-tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 44; application/pdf |
| اللغة: | English |
| تدمد: | 0009-9104 1365-2249 |
| العلاقة: | Clinical and experimental immunology, 2020, 200 (1), pp. 33 - 44; https://repository.icr.ac.uk/handle/internal/3549Test |
| DOI: | 10.1111/cei.13403 |
| الإتاحة: | https://doi.org/10.1111/cei.13403Test https://repository.icr.ac.uk/handle/internal/3549Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.5362EA8 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00099104 13652249 |
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| DOI: | 10.1111/cei.13403 |