Friday, October 28, 2011
Room A2/A7 (San Jose Convention Center)
CD8+ T cells have been shown to mediate tumor control and regression. Therefore, a vaccine which elicits a robust CD8+ specific T cell response against tumor antigens could provide a therapeutic choice for many types of cancer. In an experimental melanoma peptide vaccine, two distinct CD+ T cell responses were observed, sustained and transient. Specific CD8+ T cell responses which increase in magnitude during weekly vaccinations and peak at the six week time point were considered sustained. In contrast, a transient response was characterized as a strong CD8+ T cell response at early vaccination time points, but decreased in magnitude to less than half the maximal frequency at week six. Our preliminary data demonstrated expression of killer lectin-like receptor G1 (KLRG1) in the transient CD8+ T cell response. KLRG1 expression has been shown to be a marker of T-cell exhaustion, based on previous studies demonstrating an immune dysfunction in chronic viral infections. T cell exhaustion is defined as decreases in cytotoxicity, cytokine production, and proliferative responsiveness to antigen. Therefore, the hypothesis of this project is that the transient immune response seen in a portion of the vaccinated melanoma patients is mediated by the expression of inhibitory receptors on peptide-specific CD8+ T cells. Thus, we are proposing to use novel molecular analyses to assess the phenotypic and functional differences in sustained and transient CD8+ T cell immune responses. A long term goal of this project is to use siRNA technology delivered by a transposon system to rescue this exhausted phenotype.
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