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dc.contributor.authorMussai, Francisen_UK
dc.contributor.authorEgan, Sharonen_UK
dc.contributor.authorHunter, Stuarten_UK
dc.contributor.authorWebber, Hannahen_UK
dc.contributor.authorFisher, Jonathanen_UK
dc.contributor.authorWheat, Rachelen_UK
dc.contributor.authorMcConville, Carmelen_UK
dc.contributor.authorSbirkov, Yordanen_UK
dc.contributor.authorWheeler, Kateen_UK
dc.contributor.authorBendle, Gavinen_UK
dc.contributor.authorPetrie, Kevinen_UK
dc.contributor.authorAnderson, Johnen_UK
dc.contributor.authorChesler, Louisen_UK
dc.contributor.authorDe Santo, Carmelaen_UK
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.en_UK
dc.publisherAmerican Association for Cancer Researchen_UK
dc.relationMussai F, Egan S, Hunter S, Webber H, Fisher J, Wheat R, McConville C, Sbirkov Y, Wheeler K, Bendle G, Petrie K, Anderson J, Chesler L & De Santo C (2015) Neuroblastoma arginase activity creates an immunosuppressive microenvironment impairing autologous and engineered immunity. Cancer Research, 75 (15), pp. 3043-3053.
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.en_UK
dc.titleNeuroblastoma arginase activity creates an immunosuppressive microenvironment impairing autologous and engineered immunityen_UK
dc.typeJournal Articleen_UK
dc.rights.embargoreason[Cancer Res-2015-Mussai-3043-53.pdf] The publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.en_UK
dc.citation.jtitleCancer Researchen_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationUniversity of Nottinghamen_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationUniversity College Londonen_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationUniversity of Oxforden_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
dc.contributor.affiliationBiological and Environmental Sciencesen_UK
dc.contributor.affiliationUniversity College Londonen_UK
dc.contributor.affiliationInstitute of Cancer Researchen_UK
dc.contributor.affiliationUniversity of Birminghamen_UK
rioxxterms.apcnot requireden_UK
rioxxterms.typeJournal Article/Reviewen_UK
local.rioxx.authorMussai, Francis|en_UK
local.rioxx.authorEgan, Sharon|en_UK
local.rioxx.authorHunter, Stuart|en_UK
local.rioxx.authorWebber, Hannah|en_UK
local.rioxx.authorFisher, Jonathan|en_UK
local.rioxx.authorWheat, Rachel|en_UK
local.rioxx.authorMcConville, Carmel|en_UK
local.rioxx.authorSbirkov, Yordan|en_UK
local.rioxx.authorWheeler, Kate|en_UK
local.rioxx.authorBendle, Gavin|en_UK
local.rioxx.authorPetrie, Kevin|0000-0002-9805-9152en_UK
local.rioxx.authorAnderson, John|en_UK
local.rioxx.authorChesler, Louis|en_UK
local.rioxx.authorDe Santo, Carmela|en_UK
local.rioxx.projectInternal Project|University of Stirling|
local.rioxx.filenameCancer Res-2015-Mussai-3043-53.pdfen_UK
Appears in Collections:Biological and Environmental Sciences Journal Articles

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