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Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM

Publication ,  Journal Article
Beck, B; Gillespie, GY; Lopez, RD; Cloud, GA; Langford, C; Kim, H; Harkins, L; Lamb, LS
Published in: Cancer Research
April 15, 2012

Glioblastoma multiforme (GBM) remains frustratingly impervious to any existing therapy. We have previously shown that GBM is sensitive to recognition and lysis by ex vivo activated γδ T cells, a minor subset of lymphocytes that innately recognize autologous stress-associated target antigens via the T cell receptor and/or NKG2D. However, circulating γδ T cell counts and function are significantly reduced in patients with GBM. We sought to determine the role of γδ T cells in the immune response to high-grade gliomas in C57BL/6 mice bearing GL261 cell line-derived intracranial gliomas. Examination of mice 15 days after intracranial tumor placement and prior to development of neurologic symptoms revealed small infiltrating high-grade gliomas near the injection site. Concurrently, the peripheral blood γδ T cell count was significantly increased when compared to control mice that received only the methylcellulose vehicle (p=0.0003). T cell expansion was confined to the γδ T cell compartment, and a substantial proportion of γδ T cells in tumor-bearing mice expressed Annexin-V (20%-45%) indicating progression to apoptosis. Annexin-V expression in control mice was confined to 2-5% of γδ T cells, significantly less than tumor-bearing mice (p<0.0001). GL261-derived tumors expressed γδ T cell target stress-associated NKG2D ligands H60, MULT-1 and RAE-1, yet γδ T cells did not infiltrate the intracranial tumors. In a separate experiment, we found no survival advantage between wild-type (WT) mice over γδ T cell-deficient (C57BL/6α-/−) tumor-bearing mice. Based on this observation that activated γδ T cells did not invade the tumor, we treated mice with a stereotactic intracranial injection of 1.5 x 106 ex vivo expanded/activated γδ T cells approximately 15 minutes following placement of 5 x 106 GL261 glioma cells. Mice that received intracranial γδ T cells were protected from tumor development at site of injection, although distant tumors did eventually form. These data suggest that γδ T cells are stimulated in glioma-bearing mice and that depletion in γδ T cells observed in mouse glioma models and human GBM are likely due to activation-induced cell death in response to the tumor. Activated γδ T cells do not traffic to the tumor parenchyma; however, an antitumor effect can be achieved by direct placement of ex vivo activated γδ T cells in the vicinity of microscopic disease, suggesting a potential post-resection strategy for treatment of minimal residual GBM.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 530. doi:1538-7445.AM2012-530

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2012

Volume

72

Issue

8_Supplement

Start / End Page

530 / 530

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
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MLA
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Beck, B., Gillespie, G. Y., Lopez, R. D., Cloud, G. A., Langford, C., Kim, H., … Lamb, L. S. (2012). Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM. Cancer Research, 72(8_Supplement), 530–530. https://doi.org/10.1158/1538-7445.am2012-530
Beck, Benjamin, G Yancey Gillespie, Richard D. Lopez, Gretchen A. Cloud, Cathy Langford, Hyung Kim, Lualhati Harkins, and Lawrence S. Lamb. “Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM.” Cancer Research 72, no. 8_Supplement (April 15, 2012): 530–530. https://doi.org/10.1158/1538-7445.am2012-530.
Beck B, Gillespie GY, Lopez RD, Cloud GA, Langford C, Kim H, et al. Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM. Cancer Research. 2012 Apr 15;72(8_Supplement):530–530.
Beck, Benjamin, et al. “Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM.” Cancer Research, vol. 72, no. 8_Supplement, American Association for Cancer Research (AACR), Apr. 2012, pp. 530–530. Crossref, doi:10.1158/1538-7445.am2012-530.
Beck B, Gillespie GY, Lopez RD, Cloud GA, Langford C, Kim H, Harkins L, Lamb LS. Abstract 530: Circulating γδ T cells are activated and depleted during progression of high-grade gliomas: Implications for γδ T cells therapy of GBM. Cancer Research. American Association for Cancer Research (AACR); 2012 Apr 15;72(8_Supplement):530–530.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

April 15, 2012

Volume

72

Issue

8_Supplement

Start / End Page

530 / 530

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis