Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway

Jun Wei, Jason Barr, Ling Yuan Kong, Yongtao Wang, Adam Wu, Amit K. Sharma, Joy Gumin, Verlene Henry, Howard Colman, Waldemar Priebe, Raymond Sawaya, Frederick F. Lang, Amy B. Heimberger

Research output: Contribution to journalArticlepeer-review

229 Scopus citations

Abstract

Glioblastoma multiforme (GBM) is a lethal cancer that responds poorly to radiotherapy and chemotherapy. Glioma cancer-initiating cells have been shown to recapitulate the characteristic features of GBM and mediate chemotherapy and radiation resistance. However, it is unknown whether the cancer-initiating cells contribute to the profound immune suppression in GBM patients. Recent studies have found that the activated form of signal transducer and activator of transcription 3 (STAT3) is a key mediator in GBM immunosuppression. We isolated and generated CD133+ cancer-initiating single colonies from GBM patients and investigated their immune-suppressive properties.We found that the cancer-initiating cells inhibited T-cell proliferation and activation, induced regulatory Tcells, and triggered T-cell apoptosis. The STAT3 pathway is constitutively active in these clones and the immunosuppressive properties were markedly diminished when the STAT3 pathway was blocked in the cancer-initiating cells. These findings indicate that cancer-initiating cells contribute to the immune evasion of GBM and that blockade of the STAT3 pathway has therapeutic potential.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalMolecular cancer therapeutics
Volume9
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway'. Together they form a unique fingerprint.

Cite this