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  1. W. Kim1,
  2. R. M. Prins1,2,
  3. L. M. Liau1,3
  1. 1Department of Surgery, Division of Neurosurgery
  2. 2Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA
  3. 3Jonsson Comprehensive Cancer Center and Brain Research Institute, Los Angeles, CA.


Despite recent advances in chemotherapy, radiation treatment, and surgical interventions for brain tumors, the associated prognoses still remain very poor. Immunolotherapeutic techniques have thus emerged as a favorable solution on account of their high specificity for destroying tumor cells while relatively sparing normal brain tissue. However, to achieve cell-specific cytotoxic lysing, a viable molecular target must be expressed at immunologically relevant levels on the surface of the tumor cells. Although some candidate targets have been identified in brain tumors, their levels of expression are too low to induce an effective immune response. To test the potential utility of the melanoma-associated antigen (MAA), gp100, we have shown that the addition of IFN-γ can increase the surface presentation of this MAA, and subsequently gp100-specific T cell-mediated cell death, via up-regulating tumor cell MHC expression. An alternate method of increasing the surface presentation of a cancer antigen is to increase its intracellular expression. We used a DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine to reverse possible gp100 promoter methylation that may interfere with adequate gene expression. In addition, we assessed the effects of a histone deacetylase inhibitor (HDACi) in augmenting the effects of the demethylating agent in unsilencing the transcription of these antigens. Cells were incubated with their appropriate agents for 72 hours, followed by total RNA extraction and reverse transcription PCR. Our results suggest that gp100 expression may not be mediated by epigenetic regulation; however, recent studies have shown that the use of demethylating agents and HDAC inhibitors can sensitize tumor cells to CTL-mediated killing by an unknown mechanism, calling for future studies to investigate this phenomenon.

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