Analysis of tumor cell death on antigen-specific immune responses

Division Of Basic Sciences - Nci

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Abstract

The way in which tumor cells die is proposed to have a substantial impact on the generation of adaptive immune responses. In our previous studies we have been able to demonstrate that induction of apoptosis versus necrosis in subcutaneously growing tumors has profoundly different effects on tumor specific CD8+ T cells. While apoptotic tumor cell death promote anti-tumor immune responses necrotic tumor cell death impair these responses. Based on these in vivo findings we have been able to establish an in vitro system, which allows to dissect the immunological mechanisms responsible for these observations in more detail. We have been able to dissect on a molecular level how antigens from dying cells are being cross-presented by professional antigen presenting cells such as dendritic cells in vitro. More importantly we have identified different proteins, which either support or impair the presentation of antigens from dying cells. Ultimately our findings will help enhance immune responses against cancer cells