Glioblastoma Cancer-Initiating Cells Inhibit T-Cell Proliferation and Effector Responses by the Signal Transducers and Activators of Transcription 3 Pathway

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

来源：Molecular Cancer Therapeutics, 2010, 9(1): 67-78.

DOI：10.1158/1535-7163.MCT-09-0734

• NEURAL STEM-CELLS
• GROWTH-FACTOR
• MOLECULAR TARGETS
• GENE-EXPRESSION
• GLIOMA-CELLS
• STAT3
• INTERLEUKIN-10
• LYMPHOCYTES
• MECHANISMS
• APOPTOSIS

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. Mol Cancer Ther; 9(1); 67-78.

• 出版日期2010-1