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Appears in Collections:Biological and Environmental Sciences Journal Articles
Peer Review Status: Refereed
Title: Neuroblastoma arginase activity creates an immunosuppressive microenvironment impairing autologous and engineered immunity
Authors: Mussai, Francis
Egan, Sharon
Hunter, Stuart
Webber, Hannah
Fisher, Jonathan
Wheat, Rachel
McConville, Carmel
Sbirkov, Yordan
Wheeler, Kate
Bendle, Gavin
Petrie, Kevin
Anderson, John
Chesler, Louis
De, Santo Carmela
Contact Email:
Issue Date: 1-Aug-2015
Publisher: American Association for Cancer Research
Citation: Mussai 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.
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.
Type: Journal Article
DOI Link:
Rights: The 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.
Affiliation: University of Birmingham
University of Nottingham
University of Birmingham
Institute of Cancer Research
University College London
University of Birmingham
University of Birmingham
Institute of Cancer Research
University of Oxford
University of Birmingham
Biological and Environmental Sciences
University College London
Institute of Cancer Research
University of Birmingham

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