title: Glioblastoma cancer-initiating cells inhibit T-cell proliferation and effector responses by the signal transducers and activators of transcription 3 pathway.
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 T cells, 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.
authors.affiliation: Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1402, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wei
authors.forename: Jason
authors.initials: J
authors.lastname: Barr
authors.forename: Ling-Yuan
authors.initials: LY
authors.lastname: Kong
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Wang
authors.forename: Adam
authors.initials: A
authors.lastname: Wu
authors.forename: Amit K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Joy
authors.initials: J
authors.lastname: Gumin
authors.forename: Verlene
authors.initials: V
authors.lastname: Henry
authors.forename: Howard
authors.initials: H
authors.lastname: Colman
authors.forename: Waldemar
authors.initials: W
authors.lastname: Priebe
authors.forename: Raymond
authors.initials: R
authors.lastname: Sawaya
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D018925:Chemokines / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D018925:Chemokines; D010750:Phosphoproteins; D050796:STAT3 Transcription Factor