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dc.contributor.authorMussai, Fen_US
dc.contributor.authorEgan, Sen_US
dc.contributor.authorHunter, Sen_US
dc.contributor.authorWebber, Hen_US
dc.contributor.authorFisher, Jen_US
dc.contributor.authorWheat, Ren_US
dc.contributor.authorMcConville, Cen_US
dc.contributor.authorSbirkov, Yen_US
dc.contributor.authorWheeler, Ken_US
dc.contributor.authorBendle, Gen_US
dc.contributor.authorPetrie, Ken_US
dc.contributor.authorAnderson, Jen_US
dc.contributor.authorChesler, Len_US
dc.contributor.authorDe Santo, Cen_US
dc.date.accessioned2020-07-24T15:02:07Z
dc.date.issued2015-08
dc.identifier.citationCancer research, 2015, 75 (15), pp. 3043 - 3053
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3866
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-14-3443
dc.description.abstractNeuroblastoma is the most common extracranial solid tumor of childhood, and survival remains poor for patients with advanced disease. Novel immune therapies are currently in development, but clinical outcomes have not matched preclinical results. Here, we describe key mechanisms in which neuroblastoma inhibits the immune response. We show that murine and human neuroblastoma tumor cells suppress T-cell proliferation through increased arginase activity. Arginase II is the predominant isoform expressed and creates an arginine-deplete local and systemic microenvironment. Neuroblastoma arginase activity results in inhibition of myeloid cell activation and suppression of bone marrow CD34(+) progenitor proliferation. Finally, we demonstrate that the arginase activity of neuroblastoma impairs NY-ESO-1-specific T-cell receptor and GD2-specific chimeric antigen receptor-engineered T-cell proliferation and cytotoxicity. High arginase II expression correlates with poor survival for patients with neuroblastoma. The results support the hypothesis that neuroblastoma creates an arginase-dependent immunosuppressive microenvironment in both the tumor and blood that leads to impaired immunosurveillance and suboptimal efficacy of immunotherapeutic approaches.
dc.formatPrint-Electronic
dc.format.extent3043 - 3053
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectNeuroblastoma
dc.subjectNeoplasms, Experimental
dc.subjectArginase
dc.subjectGangliosides
dc.subjectArginine
dc.subjectMembrane Proteins
dc.subjectReceptors, Antigen, T-Cell
dc.subjectRecombinant Proteins
dc.subjectAntigens, Neoplasm
dc.subjectLymphocyte Activation
dc.subjectCell Proliferation
dc.subjectTumor Microenvironment
dc.titleNeuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity.
dc.typeJournal Article
dcterms.dateAccepted2015-05-09
rioxxterms.versionofrecord10.1158/0008-5472.can-14-3443
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2015-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue15
pubs.notesNot known
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.publication-statusPublished
pubs.volume75
pubs.embargo.termsNot known
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
dc.contributor.icrauthorChesler, Louisen
dc.contributor.icrauthorPetrie, Kevinen
dc.contributor.icrauthorSbirkov, Yordanen


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