Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are believed to be involved in the regulation of immunogenic cell death in cancer cells following high-dose radiation therapy (RT)(1,2). In addition, recent evidence from our group suggests that the IRE-1a/XBP-1 branch of the UPR plays a crucial role in the antigen presentation of dead cells by CD8A+ dendritic cells (DCs)(3). In this project, we therefore hypothesize that the UPR is a significant component of the protective anti-tumor immune response after high dose RT. Using transgenic mice and models of melanoma and renal cell carcinoma, we will unravel how the UPR in DCs or tumor cells is involved in the therapeutic effects of RT and how the UPR can be exploited for improving the success of RT.