642 Repurposing bortezomib for improved treatment of melanoma by exploiting immunogenic cell death

Abstract

Immunogenic cell death (ICD) constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies. Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as the proteasome inhibitor bortezomib, as demonstrated in malignant myeloma and mantle cell lymphoma, but not yet in melanoma. We have shown in melanoma that bortezomib induces NOXA-dependent apoptosis. Here, we show that bortezomib indeed causes ICD in vitro through induction of endoplasmic reticulum stress, autophagy and apoptosis and through translocation and/or secretion of damage-associated molecular patterns (DAMPs).