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Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma.

Publication ,  Journal Article
Bryant, NL; Suarez-Cuervo, C; Gillespie, GY; Markert, JM; Nabors, LB; Meleth, S; Lopez, RD; Lamb, LS
Published in: Neuro Oncol
August 2009

Classical immunotherapeutic approaches to glioblastoma multiforme (GBM) have shown mixed results, and therapies focused on innate lymphocyte activity against GBM have not been rigorously evaluated. We examined peripheral blood lymphocyte phenotype, gammadelta T-cell number, mitogenic response, and cytotoxicity against GBM cell lines and primary tumor explants from GBM patients at selected time points prior to and during GBM therapy. Healthy volunteers served as controls and were grouped by age. T-cell infiltration of tumors from these patients was assessed by staining for CD3 and T-cell receptor gammadelta. Our findings revealed no differences in counts of mean absolute T-cells, T-cell subsets CD3+CD4+ and CD3+CD8+, and natural killer cells from healthy volunteers and patients prior to and immediately after GBM resection. In contrast, gammadelta T-cell counts and mitogen-stimulated proliferative response of gammadelta T-cells were markedly decreased prior to GBM resection and throughout therapy. Expanded/activated gammadelta T-cells from both patients and healthy volunteers kill GBM cell lines D54, U373, and U251, as well as primary GBM, without cytotoxicity to primary astrocyte cultures. Perivascular T-cell accumulation was noted in paraffin sections, but no organized T-cell invasion of the tumor parenchyma was seen. Taken together, these data suggest that gammadelta T-cell depletion and impaired function occur prior to or concurrent with the growth of the tumor. The significant cytotoxicity of expanded/activated gammadelta T-cells from both healthy controls and selected patients against primary GBM explants may open a previously unexplored approach to cellular immunotherapy of GBM.

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Published In

Neuro Oncol

DOI

ISSN

1522-8517

Publication Date

August 2009

Volume

11

Issue

4

Start / End Page

357 / 367

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Phenotype
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Immunoenzyme Techniques
  • Humans
  • Glioblastoma
 

Citation

APA
Chicago
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MLA
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Bryant, N. L., Suarez-Cuervo, C., Gillespie, G. Y., Markert, J. M., Nabors, L. B., Meleth, S., … Lamb, L. S. (2009). Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma. Neuro-Oncology, 11(4), 357–367. https://doi.org/10.1215/15228517-2008-111
Bryant, Nichole L., Catalina Suarez-Cuervo, G Yancey Gillespie, James M. Markert, L Burt Nabors, Sreelatha Meleth, Richard D. Lopez, and Lawrence S. Lamb. “Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma.Neuro-Oncology 11, no. 4 (August 2009): 357–67. https://doi.org/10.1215/15228517-2008-111.
Bryant NL, Suarez-Cuervo C, Gillespie GY, Markert JM, Nabors LB, Meleth S, et al. Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma. Neuro-oncology. 2009 Aug;11(4):357–67.
Bryant, Nichole L., et al. “Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma.Neuro-Oncology, vol. 11, no. 4, Aug. 2009, pp. 357–67. Epmc, doi:10.1215/15228517-2008-111.
Bryant NL, Suarez-Cuervo C, Gillespie GY, Markert JM, Nabors LB, Meleth S, Lopez RD, Lamb LS. Characterization and immunotherapeutic potential of gammadelta T-cells in patients with glioblastoma. Neuro-oncology. 2009 Aug;11(4):357–367.
Journal cover image

Published In

Neuro Oncol

DOI

ISSN

1522-8517

Publication Date

August 2009

Volume

11

Issue

4

Start / End Page

357 / 367

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • T-Lymphocytes
  • Receptors, Antigen, T-Cell, gamma-delta
  • Phenotype
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Immunoenzyme Techniques
  • Humans
  • Glioblastoma