Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Shimato, S; Maier, LM; Maier, R; Bruce, JN; Anderson, RC; Anderson, DE.
Profound tumor-specific Th2 bias in patients with malignant glioma.
BMC Cancer. 2012; 12(4):561-561
Doi: 10.1186/1471-2407-12-561
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- Co-Autor*innen der Med Uni Graz
- Maier Richard
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- 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 alpha 2 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-gamma and IL-5 levels, and the ratio of IFN-gamma/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-13R alpha 2 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-gamma/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.
- Find related publications in this database (using NLM MeSH Indexing)
- Aged -
- Antigens, Neoplasm - immunology
- Brain Neoplasms - blood
- Cytokines - analysis
- Enzyme-Linked Immunosorbent Assay -
- Epitopes, T-Lymphocyte - immunology
- Female -
- Glioma - blood
- Histocompatibility Antigens Class II - immunology
- Humans -
- Male -
- Middle Aged -
- Th2 Cells - immunology