title: Profound tumor-specific Th2 bias in patients with malignant glioma.
abstract: BACKGROUND
  Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4+ helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4+ helper T cell responses in the peripheral blood of patients with malignant gliomas.
  
  
  METHODS
  Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias.
  
  
  RESULTS
  We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs.
  
  
  CONCLUSIONS
  Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically.
authors.affiliation: Department of Neurosurgery, Gabriele Bartoli Brain Tumor Research Laboratory, Columbia University, New York City, NY, USA.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimato
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Maier
authors.forename: Richard
authors.initials: R
authors.lastname: Maier
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.forename: Richard C E
authors.initials: RC
authors.lastname: Anderson
authors.forename: David E
authors.initials: DE
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D001932:Brain Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005910:Glioma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II