Neo-antigens derived from apoptotic tumour cells are sensed by the immune system and drive effective antitumour immunity. This ‘immunogenic cell death’ (ICD) can be elicited in vivo following bortezomib (26S proteasome inhibitor) treatment in some cancers. Here, we test the dynamics of bortezomib-induced ER stress and apoptosis in melanoma and whether this promotes ICD in the tumour microenvironment. We first confirmed that a clinically-relevant dose of bortezomib induced hallmarks of ICD in vitro. Necessary markers of ICD, including cell-surface expression of calreticulin, HSP70 and HSP90, were upregulated following bortezomib treatment in human and murine melanoma. The secretion of HMGB1 and ATP by apoptotic melanoma cells was also detected, further suggesting ICD initiation. We confirmed bortezomib-induced ER stress by real-time imaging of a ER stress biosensor in melanoma cells. We next asked whether bortezomib-treated melanoma cells could elicit anti-tumour immunity in vivo. Mice were primed subcutaneously with predetermined conditions of melanoma cells that are undergoing ICD. Mice were then challenged a week later on the opposing flank with matched, live melanoma cells and tumour growth was monitored. We observed a delay in tumour growth and decreased tumour volume in mice that were primed by ICD compared to controls. Together these data demonstrate that melanoma cells undergo ICD following bortezomib treatment and this cellular stress can be co-opted to enable effective anti-tumour immunity. Next we will use this vaccination method to further determine the effects on the innate immune system. ICD induction could be a beneficial therapeutic method to further potentiate patient responses.