dc.contributor.author | Mussai, F | |
dc.contributor.author | Egan, S | |
dc.contributor.author | Hunter, S | |
dc.contributor.author | Webber, H | |
dc.contributor.author | Fisher, J | |
dc.contributor.author | Wheat, R | |
dc.contributor.author | McConville, C | |
dc.contributor.author | Sbirkov, Y | |
dc.contributor.author | Wheeler, K | |
dc.contributor.author | Bendle, G | |
dc.contributor.author | Petrie, K | |
dc.contributor.author | Anderson, J | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | De Santo, C | |
dc.date.accessioned | 2020-07-24T15:02:07Z | |
dc.date.issued | 2015-08-01 | |
dc.identifier.citation | Cancer research, 2015, 75 (15), pp. 3043 - 3053 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3866 | |
dc.identifier.eissn | 1538-7445 | |
dc.identifier.doi | 10.1158/0008-5472.can-14-3443 | |
dc.description.abstract | Neuroblastoma 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.format | Print-Electronic | |
dc.format.extent | 3043 - 3053 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Neuroblastoma | |
dc.subject | Neoplasms, Experimental | |
dc.subject | Arginase | |
dc.subject | Gangliosides | |
dc.subject | Arginine | |
dc.subject | Membrane Proteins | |
dc.subject | Receptors, Antigen, T-Cell | |
dc.subject | Recombinant Proteins | |
dc.subject | Antigens, Neoplasm | |
dc.subject | Lymphocyte Activation | |
dc.subject | Cell Proliferation | |
dc.subject | Tumor Microenvironment | |
dc.title | Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-05-09 | |
rioxxterms.versionofrecord | 10.1158/0008-5472.can-14-3443 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer research | |
pubs.issue | 15 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 75 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | |
dc.contributor.icrauthor | Sbirkov, Yordan | |
dc.contributor.icrauthor | Petrie, Kevin | |
dc.contributor.icrauthor | Chesler, Louis | |