Analysis of tumor cell death on antigen-specific immune responses

肿瘤细胞死亡的方式被认为对适应性免疫反应的产生有重大影响。在我们之前的研究中，我们已经能够证明，在皮下生长的肿瘤中，诱导凋亡和坏死对肿瘤特异性CD8+T细胞具有截然不同的影响。而凋亡性肿瘤细胞死亡促进抗肿瘤免疫反应，而坏死性肿瘤细胞死亡则削弱这些反应。基于这些体内发现，我们已经能够建立一个体外系统，允许更详细地剖析导致这些观察的免疫学机制。我们已经能够在分子水平上剖析来自死亡细胞的抗原是如何在体外被专业的抗原提呈细胞(如树突状细胞)交叉提呈的。更重要的是，我们已经确定了不同的蛋白质，这些蛋白质要么支持，要么损害死亡细胞的抗原呈递。最终，我们的发现将有助于增强对癌细胞的免疫反应

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