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


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 anti-tumor 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 pro-inflammatory 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.

DOI: 10.1007/s11060-012-0981-6

4 Figures and Tables

Citations per Year

455 Citations

Semantic Scholar estimates that this publication has 455 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{See2012TheRO, title={The role of STAT3 activation in modulating the immune microenvironment of GBM}, author={Alfred P See and James E. Han and Jillian Phallen and Zev A. Binder and Gary L. Gallia and Fan Pan and Dilini Jinasena and Christopher M. Jackson and Zineb Belcaid and Sung Jin Jeong and Chelsea Gottschalk and Jing Zeng and Jacob Ruzevick and Sarah Nicholas and Young Joon Kim and Emilia Albesiano and Drew M . Pardoll and Michael K. Lim}, journal={Journal of Neuro-Oncology}, year={2012}, volume={110}, pages={359-368} }