Introduction Treatment of advanced prostate cancer with chemotherapy can be toxic in a generally elderly population. Immunotherapy, with potentially fewer side effects has recently gained renewed interest. Our laboratory has investigated the receptor NKG2D on NK cells and gamma delta T cells. This receptor can be activated by cells expressing NKG2D ligands, found on prostate cancer cells but only in limited amounts on healthy cells. We have shown that patients with prostate cancer receiving concomitant therapies display a significant impairment in the NKG2D pathway, although this potentially can be boosted, suggesting therapeutic application. Aim and objectives This project will explore the NKG2D pathway as part of the lymphoid stress surveillance in prostate cancer. The following questions will be addressed: 1) Is there evidence that the NKG2D pathway varies with tumour stage in patients with prostate cancer? 2) Is there evidence that the NKG2D pathway varies with concomitant therapy in patients with prostate cancer and is this correlated with altered killing potential? 3) Are we able to influence to variability of PBMC responses to NKG2D ligand + targets? Methods Experimental set up includes gene expression analysis on prostate cancer tissue examining components of the NKG2D axis. Patient blood samples to monitor the NKG2D pathway during various therapies. Flow cytometry for phenotypical and functional analysis. Co-culture experiments with peripheral blood mononuclear cells and NKG2D ligand + cell lines will be used in order to optimise the NKG2D pathway. Scientific and medical opportunities Exploration of the NKG2D-ligand interaction under various tumour and host conditions will help our understanding of this axis as a target for immune therapy, which ultimately could benefit patients.