Priming of protective T cell responses against virus-induced tumors in mice with human immune system components

Many pathogens that cause human disease infect only humans. To identify the mechanisms of immune protection against these pathogens and also to evaluate promising vaccine candidates, a small animal model would be desirable. We demonstrate that primary T cell responses in mice with reconstituted human immune system components control infection with the oncogenic and persistent Epstein-Barr virus (EBV). These cytotoxic and interferon-γ–producing T cell responses were human leukocyte antigen (HLA) restricted and specific for EBV-derived peptides. In HLA-A2 transgenic animals and similar to human EBV carriers, T cell responses against lytic EBV antigens dominated over recognition of latent EBV antigens. T cell depletion resulted in elevated viral loads and emergence of EBV-associated lymphoproliferative disease. Both loss of CD4+ and CD8+ T cells abolished immune control. Therefore, this mouse model recapitulates features of symptomatic primary EBV infection and generates T cell–mediated immune control that resists oncogenic transformation

JAGGED1 Espression is Associated with Prostate Cancer Metastasis and Recurrence

Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters. These findings support a model in which dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers

Defining Aggressive Prostate Cancer Using a 12 Gene Model

The critical clinical question in prostate cancer research is to develop means of distinguishing aggressive from indolent disease. Using a combination of proteomic and expression array data, we identified a set of 40 genes with concordant dysregulation of protein products that could be evaluated in situ by quantitative immunohistochemistry. Using linear discriminant analysis, we determined that the optimal model to predict prostate cancer progression consisted of 12 proteins. Using a separate patient population, the transcriptional levels of the 12 genes encoding for these proteins predicted PSAfailure in 79 men following surgery for clinically localized prostate cancer (p=0.0015). This study demonstrates that cross platform models can lead to predictive models with the possible advantage of being more robust through this selection proces