The role of STAT3 activation in modulating the immune microenvironment of GBM

Alfred P. See, James E. Han, Jillian Phallen, Zev Binder, Gary Gallia, Fan Pan, Dilini Jinasena, Christopher Jackson, Zineb Belcaid, Sung Jin Jeong, Chelsea Gottschalk, Jing Zeng, Jacob Ruzevick, Sarah Nicholas, Young Kim, Emilia Albesiano, Drew M. Pardoll, Michael Lim

Research output: Contribution to journalArticle

Abstract

Glioblastoma multiforme (GBM) modulates the immune system to engance its malignant potential. Signal transducer and activator of transcription 3 (STAT3) activation is a regulatory node in modulating the immune microenvironment in several human tumors, including GBM. To investigate whether STAT3 inhibition might enhance antitumor responses, we inhibited STAT3 signaling using small interfering RNA against STAT3. We tested the human GBM cell lines U87, U251, and HS683, which are known to constitutively express high levels of phospho-STAT3. STAT3 inhibition resulted in enhanced expression of several proinflammatory cytokines and chemokines and supernatants from STAT3-silenced human GBM cell lines increased lipopolysaccharide-induced dendritic cell activation in vitro. We obtained comparable results when STAT3 activity was suppressed with specific small molecule inhibitors. Our results support the hypothesis that activated STAT3 contributes to the immunosuppressive microenvironment in GBM and support previous studies implicating STAT3 as a potential target for immunotherapy.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalJournal of neuro-oncology
Volume110
Issue number3
DOIs
StatePublished - Dec 1 2012

Keywords

  • Glioblastoma multiforme (GBM)
  • Immunotherapy
  • Signal transducer and activator of transcription 3 (STAT3)
  • Small molecule inhibitor

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

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  • Cite this

    See, A. P., Han, J. E., Phallen, J., Binder, Z., Gallia, G., Pan, F., Jinasena, D., Jackson, C., Belcaid, Z., Jeong, S. J., Gottschalk, C., Zeng, J., Ruzevick, J., Nicholas, S., Kim, Y., Albesiano, E., Pardoll, D. M., & Lim, M. (2012). The role of STAT3 activation in modulating the immune microenvironment of GBM. Journal of neuro-oncology, 110(3), 359-368. https://doi.org/10.1007/s11060-012-0981-6