Immunomodulation mediated by anti-angiogenic therapy improves CD8 T cell immunity against experimental glioma

Courtney S. Malo, Roman H. Khadka, Katayoun Ayasoufi, Fang Jin, Jackson E. AbouChehade, Michael J. Hansen, Raymond Iezzi, Kevin D. Pavelko, Aaron J. Johnson

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM.

Original languageEnglish (US)
Article number320
JournalFrontiers in Oncology
Volume8
Issue numberAUG
DOIs
StatePublished - Aug 20 2018

Keywords

  • Anti-angiogenic therapy
  • Combination therapy
  • Glioblastoma
  • Immunotherapy
  • Vaccine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Malo, C. S., Khadka, R. H., Ayasoufi, K., Jin, F., AbouChehade, J. E., Hansen, M. J., Iezzi, R., Pavelko, K. D., & Johnson, A. J. (2018). Immunomodulation mediated by anti-angiogenic therapy improves CD8 T cell immunity against experimental glioma. Frontiers in Oncology, 8(AUG), [320]. https://doi.org/10.3389/fonc.2018.00320