Harnessing immunogenic cell death mechanisms to trigger antitumour immunity

死亡不是终点，而是垂死细胞和免疫系统细胞之间新的通信轴的开始。细胞死亡的方式极大地改变了释放的危险信号。虽然细胞凋亡倾向于免疫沉默的结果，非凋亡形式的细胞死亡，如半胱天冬酶非依赖性坏死性凋亡，可以是高度免疫原性的。成功的博士候选人将研究如何非凋亡细胞死亡机制可以用来打开一个新的通信线路与免疫细胞。具体而言，他/她将使用ICR开发的PROTAC降解剂与放射治疗相结合，将细胞死亡信号通路重新连接为非半胱天冬酶依赖的细胞死亡形式。我们将测试通过非凋亡形式的细胞死亡杀死癌细胞是否更有效地驱动针对肿瘤的免疫反应，从而提高放射治疗的有效性。

Death is not an endpoint, but the beginning of a novel communication axis between dying cells and cells of the immune system. The way in which a cell dies dramatically alters the danger signals that get released. While apoptosis tilts towards an immunologic silent outcome, non-apoptotic forms of cell death, such as caspase-independent necroptosis, can be highly immunogenic. The successful PhD candidate will investigate how non-apoptotic cell death mechanisms can be used to open a new line of communication with immune cells. Specifically, he/she will use ICR-developed PROTAC degraders in combination with radiation therapy to rewire cell death signalling pathways into caspaseindependent forms of cell death. We will test whether killing cancer cells by non-apoptotic forms of cell death more effectively drives an immune response against tumours, hence enhancing the effectiveness of radiotherapy.