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dc.contributor.authorClose, HJen_US
dc.contributor.authorStead, LFen_US
dc.contributor.authorNsengimana, Jen_US
dc.contributor.authorReilly, KAen_US
dc.contributor.authorDroop, Aen_US
dc.contributor.authorWurdak, Hen_US
dc.contributor.authorMathew, RKen_US
dc.contributor.authorCorns, Ren_US
dc.contributor.authorNewton-Bishop, Jen_US
dc.contributor.authorMelcher, AAen_US
dc.contributor.authorShort, SCen_US
dc.contributor.authorCook, GPen_US
dc.contributor.authorWilson, EBen_US
dc.date.accessioned2020-03-16T10:38:15Z
dc.date.issued2020-04en_US
dc.identifier.citationClinical and experimental immunology, 2020, 200 (1), pp. 33 - 44en_US
dc.identifier.issn0009-9104en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3549
dc.identifier.eissn1365-2249en_US
dc.identifier.doi10.1111/cei.13403en_US
dc.description.abstractGlioblastoma (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.en_US
dc.formatPrint-Electronicen_US
dc.format.extent33 - 44en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleExpression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-11-26en_US
rioxxterms.versionofrecord10.1111/cei.13403en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2020-04en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfClinical and experimental immunologyen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Immunotherapy/Translational Immunotherapy (TL)
pubs.publication-statusAccepteden_US
pubs.volume200en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTranslational Immunotherapyen_US
dc.contributor.icrauthorMelcher, Alanen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/