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dc.contributor.author
Kamran, Neha
dc.contributor.author
Kadiyala, Padma
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Saxena, Meghna
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Candolfi, Marianela
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dc.contributor.author
Li, Youping
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Moreno Ayala, Mariela Alejandra
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Raja, Nicholas
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Shah, Diana
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Lowenstein, Pedro R.
dc.contributor.author
Castro, Maria G.
dc.date.available
2018-12-18T20:47:32Z
dc.date.issued
2017-01
dc.identifier.citation
Kamran, Neha; Kadiyala, Padma; Saxena, Meghna; Candolfi, Marianela; Li, Youping; et al.; Immunosuppressive Myeloid Cells’ Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy; Nature Publishing Group; Molecular Therapy (print); 25; 1; 1-2017; 232-248
dc.identifier.issn
1525-0016
dc.identifier.uri
http://hdl.handle.net/11336/66713
dc.description.abstract
Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy. Our results show that MDSCs constitute >40% of the tumor-infiltrating immune cells. These cells express IL-4Rα, inducible nitric oxide synthase (iNOS), arginase, programmed death ligand 1 (PDL1), and CD80, molecules that are critically involved in antigen-specific T cell suppression. Depletion of MDSCs strongly enhanced the TK/Flt3L gene therapy-induced tumor-specific CD8 T cell response, which lead to increased median survival and percentage of long-term survivors. Also, combining PDL1 or CTLA-4 immune checkpoint blockade greatly improved the efficacy of TK/Flt3L gene therapy. Our results, therefore, indicate that blocking MDSC-mediated immunosuppression holds great promise for increasing the efficacy of gene therapy-mediated immunotherapies for GBM.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
GENE THERAPY
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GLIOMA
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IMMUNOTHERAPY
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MYELOID CELLS
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TUMOR MICROENVIRONMENT
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Neurociencias
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Immunosuppressive Myeloid Cells’ Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-10-23T19:55:58Z
dc.journal.volume
25
dc.journal.number
1
dc.journal.pagination
232-248
dc.journal.pais
Reino Unido
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dc.journal.ciudad
Londres
dc.description.fil
Fil: Kamran, Neha. The University of Michigan School of Medicine; Estados Unidos
dc.description.fil
Fil: Kadiyala, Padma. The University of Michigan School of Medicine; Estados Unidos
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Fil: Saxena, Meghna. The University of Michigan School of Medicine; Estados Unidos
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Fil: Candolfi, Marianela. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
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Fil: Li, Youping. The University of Michigan School of Medicine; Estados Unidos
dc.description.fil
Fil: Moreno Ayala, Mariela Alejandra. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. The University of Michigan School of Medicine; Estados Unidos
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Fil: Raja, Nicholas. The University of Michigan School of Medicine; Estados Unidos
dc.description.fil
Fil: Shah, Diana. The University of Michigan School of Medicine; Estados Unidos
dc.description.fil
Fil: Lowenstein, Pedro R.. The University of Michigan School of Medicine; Estados Unidos
dc.description.fil
Fil: Castro, Maria G.. The University of Michigan School of Medicine; Estados Unidos
dc.journal.title
Molecular Therapy (print)
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1016/j.ymthe.2016.10.003
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info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S1525001616453505
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info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363306/
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