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Open Access Research article

Profound tumor-specific Th2 bias in patients with malignant glioma

Shinji Shimato1, Lisa M Maier2, Richard Maier3, Jeffrey N Bruce1, Richard CE Anderson1 and David E Anderson2*

Author Affiliations

1 Department of Neurosurgery, Gabriele Bartoli Brain Tumor Research Laboratory, Columbia University, New York City, NY, USA

2 Erinyes Biotechnologies, Inc, Boston, MA, USA

3 Department of Ophthalmology, Medical University of Graz, Graz, Austria

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BMC Cancer 2012, 12:561  doi:10.1186/1471-2407-12-561

Published: 27 November 2012

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.