Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors
AffiliationDepartment of Child Health, University of Arizona College of Medicine
MetadataShow full item record
CitationHajji, N., Garcia-Revilla, J., Soto, M. S., Perryman, R., Symington, J., Quarles, C. C., Healey, D. R., Guo, Y., Orta-Vázquez, M. L., Mateos-Cordero, S., Shah, K., Bomalaski, J., Anichini, G., Tzakos, A. G., Crook, T., O’Neill, K., Scheck, A. C., Venero, J. L., & Syed, N. (2022). Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors. The Journal of Clinical Investigation.
RightsCopyright © 2022, Hajji et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractNew approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1-positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as Copyright © 2022, Hajji et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
- Efficacy of arginine depletion by ADI-PEG20 in an intracranial model of GBM.
- Authors: Przystal JM, Hajji N, Khozoie C, Renziehausen A, Zeng Q, Abaitua F, Hajitou A, Suwan K, Want E, Bomalaski J, Szlosarek P, O'Neill K, Crook T, Syed N
- Issue date: 2018 Dec 13
- Arginine deprivation by arginine deiminase of Streptococcus pyogenes controls primary glioblastoma growth in vitro and in vivo.
- Authors: Fiedler T, Strauss M, Hering S, Redanz U, William D, Rosche Y, Classen CF, Kreikemeyer B, Linnebacher M, Maletzki C
- Issue date: 2015
- The Combination of Arginine Deprivation and 5-Fluorouracil Improves Therapeutic Efficacy in Argininosuccinate Synthetase Negative Hepatocellular Carcinoma.
- Authors: Thongkum A, Wu C, Li YY, Wangpaichitr M, Navasumrit P, Parnlob V, Sricharunrat T, Bhudhisawasdi V, Ruchirawat M, Savaraj N
- Issue date: 2017 Jun 1
- Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20).
- Authors: Burrows N, Cane G, Robson M, Gaude E, Howat WJ, Szlosarek PW, Pedley RB, Frezza C, Ashcroft M, Maxwell PH
- Issue date: 2016 Mar 14
- Targeted cellular metabolism for cancer chemotherapy with recombinant arginine-degrading enzymes.
- Authors: Kuo MT, Savaraj N, Feun LG
- Issue date: 2010 Aug